Vaccines

12 pages, 2101 KiB

Open AccessEditor’s ChoiceArticle

Cemiplimab in Ultra-Octogenarian Patients with Cutaneous Squamous Cell Carcinoma: The Real-Life Experience of a Tertiary Referral Center

by Nerina Denaro, Emanuela Passoni, Alice Indini, Gianluca Nazzaro, Giada Anna Beltramini, Valentina Benzecry, Giuseppe Colombo, Carolina Cauchi, Cinzia Solinas, Mario Scartozzi, Angelo Valerio Marzano and Ornella Garrone

Vaccines 2023, 11(9), 1500; https://doi.org/10.3390/vaccines11091500 - 18 Sep 2023

Cited by 4 | Viewed by 2155

Abstract

Background: The incidence of cutaneous squamous cell carcinoma (cSCC) is rapidly increasing, paralleling the aging of the population. cSCC predominantly affects chronically sun-exposed areas, such as the head and neck region. At our tertiary center, a multidisciplinary approach to non-melanoma skin cancer is [...] Read more.

Background: The incidence of cutaneous squamous cell carcinoma (cSCC) is rapidly increasing, paralleling the aging of the population. cSCC predominantly affects chronically sun-exposed areas, such as the head and neck region. At our tertiary center, a multidisciplinary approach to non-melanoma skin cancer is provided for locally advanced cSCC. Methods: We retrospectively revised all patients with locally advanced/metastatic cSCC treated with anti-PD1 antibody (Cemiplimab) at our Institution from January 2020 to March 2023 (minimum follow-up of 4 months on treatment). Results: Overall, we consecutively treated 20 ultra-octogenarian patients, of whom 15 were males and 5 were females (median age: 86.9 years). Despite age, a median number of concomitant drugs, and comorbidities, efficacy, and safety were superimposable with the available literature. No patients reported treatment-related adverse events of grade 3 or higher. Grade 2 adverse events were reported in 25% of patients. Overall, the response rate was 65%, with 50% partial responses and 20% long-lasting stable disease. The median duration of response was 14 months. The G8 elderly score was assessed in all patients, and the median score was 12 (range 9–14). Conclusions: Among ultra-octogenarian patients, a clinical benefit from Cemiplimab was obtained in most, including tumor shrinkage and pain relief. Cemiplimab confirmed its effectiveness in elderly patients in a real-life setting, with no new safety concerns. Full article

(This article belongs to the Special Issue Tumor Vaccine Development, Immune-Based Therapies and Immune Markers)

► Show Figures

Figure 1

16 pages, 318 KiB

Open AccessEditor’s ChoiceReview

A Comprehensive Review on Cancer Vaccines and Vaccine Strategies in Hepatocellular Carcinoma

by Alireza Tojjari, Ahmed Saeed, Meghana Singh, Ludimila Cavalcante, Ibrahim Halil Sahin and Anwaar Saeed

Vaccines 2023, 11(8), 1357; https://doi.org/10.3390/vaccines11081357 - 12 Aug 2023

Cited by 23 | Viewed by 5417

Abstract

HCC, the most prevalent form of primary liver cancer, presents a substantial global health challenge due to its high mortality and limited therapeutic options. This review delves into the potential of cancer vaccines as a novel therapeutic avenue for HCC. We examine the [...] Read more.

HCC, the most prevalent form of primary liver cancer, presents a substantial global health challenge due to its high mortality and limited therapeutic options. This review delves into the potential of cancer vaccines as a novel therapeutic avenue for HCC. We examine the various categories of cancer vaccines, including peptide-based, dendritic cell-based, viral vector-based, DNA, and mRNA vaccines, and their potential application in HCC management. This review also addresses the inherent challenges in vaccine development, such as tumor heterogeneity and the need for identifying tumor-specific antigens. We underscore the role of cancer vaccines in reshaping the immune environment within HCC, fostering durable immune memory, and their potential in combination therapies. The review also evaluates clinical trials and emphasizes the necessity for more extensive research to optimize vaccine design and patient selection criteria. We conclude with future perspectives, highlighting the significance of personalized therapies, innovative antigen delivery platforms, immune modulatory agents, and predictive biomarkers in revolutionizing HCC treatment. Simple Summary: This review explores the potential of cancer vaccines as a promising therapeutic strategy for hepatocellular carcinoma (HCC), a prevalent and deadly liver cancer. The authors discuss various types of cancer vaccines, their challenges, and their role in modulating the immune response within HCC. They also highlight clinical trials and future perspectives, emphasizing the importance of personalized therapies, novel antigen delivery platforms, and predictive biomarkers. The findings from this research could significantly impact the research community by providing a comprehensive understanding of the current state of cancer vaccines for HCC, thereby guiding future research and potentially transforming HCC treatment strategies. Full article

(This article belongs to the Special Issue Cancer Vaccines 3.0)

13 pages, 797 KiB

Open AccessEditor’s ChoiceArticle

Changes in Confidence, Feelings, and Perceived Necessity Concerning COVID-19 Booster

by Cheryl Lin, Brooke Bier, Ann M. Reed, John J. Paat and Pikuei Tu

Vaccines 2023, 11(7), 1244; https://doi.org/10.3390/vaccines11071244 - 15 Jul 2023

Cited by 7 | Viewed by 2538

Abstract

The COVID-19 booster first became available to all adults in the U.S. in November 2021 and a bivalent version in September 2022, but a large population remains booster-hesitant; only 17% of Americans have obtained the updated vaccine as of June 2023. We conducted [...] Read more.

The COVID-19 booster first became available to all adults in the U.S. in November 2021 and a bivalent version in September 2022, but a large population remains booster-hesitant; only 17% of Americans have obtained the updated vaccine as of June 2023. We conducted two cross-sectional surveys in 2021 and 2022 (n = 1889 and 1319) to determine whether changes in booster-related feelings or perceptions had occurred and whether they altered vaccination rates over time. We found that both positive and negative emotions had grown stronger between the two years, with the prevalence of annoyance increasing the most (21.5% to 39.7%). The impact of trust on booster intention more than doubled (OR = 7.46 to 16.04). Although perceived risk of infection decreased, more participants in 2022 indicated uncertainty or unwillingness to obtain a new booster than in 2021, while the proportion refusing a booster remained constant at 22.5%. Confidence in the COVID-19 vaccine and feelings of hope from the booster motivated acceptance; both were stronger predictors of booster receptivity than prior vaccination history. Our findings signal a need to rebuild trust by informing people of their continued risk and appealing to positive, especially optimistic emotions to encourage booster uptake. Future research should explore longitudinal trends in behavior and feelings toward new booster doses and the impact of prolonged vaccine hesitancy on infection rates. Full article

(This article belongs to the Special Issue Vaccine Hesitancy and Acceptance, Trends and Future Prospects for Public Health)

► Show Figures

Figure 1

12 pages, 286 KiB

Open AccessEditor’s ChoiceArticle

A Parent Version of the Motors of COVID-19 Vaccination Acceptance Scale for Assessing Parents’ Motivation to Have Their Children Vaccinated

by Chung-Ying Lin, Ray C. Hsiao, Yu-Min Chen and Cheng-Fang Yen

Vaccines 2023, 11(7), 1192; https://doi.org/10.3390/vaccines11071192 - 3 Jul 2023

Cited by 9 | Viewed by 2668

Abstract

Parents’ motivation to vaccinate their children against coronavirus disease 2019 (COVID-19) plays a crucial role in the uptake of COVID-19 vaccines among children. The Motors of COVID-19 Vaccination Acceptance Scale (MoVac-COVID19S) is a valuable tool for assessing individuals’ vaccination-related attitudes and the factors [...] Read more.

Parents’ motivation to vaccinate their children against coronavirus disease 2019 (COVID-19) plays a crucial role in the uptake of COVID-19 vaccines among children. The Motors of COVID-19 Vaccination Acceptance Scale (MoVac-COVID19S) is a valuable tool for assessing individuals’ vaccination-related attitudes and the factors influencing their decision to be vaccinated against COVID-19. This study adapted the MoVac-COVID19S to create a parent version (P-MoVac-COVID19S) and examined the psychometric soundness of two P-MoVac-COVID19S versions (a 9-item version (P-MoVac-COVID19S-9) and a 12-item version (P-MoVac-COVID19S-12)) for assessing parents’ motivation to vaccinate their children. A total of 550 parents completed the P-MoVac-COVID19S and a questionnaire assessing the factors that impact parents’ intention to allow their children to receive the COVID-19 vaccine using a vaccine acceptance scale. We enquired about the level of parental worry regarding the adverse effects of COVID-19 vaccines on children’s health and the number of COVID-19 vaccine doses received by parents. The factor structures of the P-MoVac-COVID19S-9 and P-MoVac-COVID19S-12 were examined using confirmatory factor analysis. The internal consistency, test–retest reliability, and concurrent validity of the P-MoVac-COVID19S were also examined. The results revealed that the P-MoVac-COVID19S-12 has a four-factor structure, which aligns well with the theoretical framework of the cognitive model of empowerment; the P-MoVac-COVID19S-9 has a one-factor structure. Both the P-MoVac-COVID19S-9 and P-MoVac-COVID19S-12 had good internal consistency and test–retest reliability and acceptable concurrent validity. The results of this study demonstrated that the P-MoVac-COVID19S is a reliable and valid instrument for assessing parent’s motivation to vaccinate their children against COVID-19. Full article

(This article belongs to the Special Issue Vaccine Hesitancy)

9 pages, 249 KiB

Open AccessEditor’s ChoiceArticle

Attitudes and Beliefs towards Rotavirus Vaccination in a Sample of Italian Women: A Cross-Sectional Study

by Giuseppe Di Martino, Riccardo Mazzocca, Laura Camplone, Fabrizio Cedrone, Pamela Di Giovanni and Tommaso Staniscia

Vaccines 2023, 11(6), 1041; https://doi.org/10.3390/vaccines11061041 - 30 May 2023

Cited by 4 | Viewed by 4251

Abstract

(1) Background: Rotavirus is the leading cause of severe diarrhea and dehydration in infants and young children worldwide. Despite the proven benefits of vaccination, vaccine hesitancy and refusal remains a significant barrier to achieving high vaccination coverage in many countries, such as Italy. [...] Read more.

(1) Background: Rotavirus is the leading cause of severe diarrhea and dehydration in infants and young children worldwide. Despite the proven benefits of vaccination, vaccine hesitancy and refusal remains a significant barrier to achieving high vaccination coverage in many countries, such as Italy. (2) Methods: An online survey was conducted among women aged between 18 and 50 years from Abruzzo Region, Italy. The survey was composed of two main sections: demographic characteristics and attitudes and knowledge about rotavirus vaccination, based on a five-point Likert scale. Logistic regression analysis was performed to evaluate factors associated with willingness to get the rotavirus vaccination. (3) Results: A total of 414 women were enrolled in the study. Women who were unaware of rotavirus more frequently had a lower education level (university degree 62.5% vs. 78.7%, p = 0.004) and reported having no children (p < 0.001). About half of the enrolled women thought that rotavirus infection is dangerous (190, 55.6%) and that rotavirus can cause a serious illness (201, 58.8%). Regarding associated factors, women informed by a physician were more likely get a vaccination compared to women informed by friends or relatives (OR 34.35, 95% CI 7.12–98.98, p < 0.001). (4) Conclusions: The present study showed low levels of knowledge and attitudes towards rotavirus vaccination. These results highlight the need for developing and improving additional public education programs for parents. Full article

(This article belongs to the Special Issue Recent Advances in Factors Associated with Vaccine Hesitancy and Acceptance)

12 pages, 2790 KiB

Open AccessEditor’s ChoiceArticle

Comparison of the Immune Effects of an mRNA Vaccine and a Subunit Vaccine against Herpes Zoster Administered by Different Injection Methods

by Kangyang Lin, Han Cao, Ning Luan, Yunfei Wang, Jingping Hu and Cunbao Liu

Vaccines 2023, 11(5), 1003; https://doi.org/10.3390/vaccines11051003 - 20 May 2023

Cited by 6 | Viewed by 4014

Abstract

Previous studies have shown that the herpes zoster subunit vaccine Shingrix™ performs well in clinical trials. However, the key ingredient in its adjuvant, QS21, is extracted from rare plants in South America, so vaccine production is limited. Compared with subunit vaccines, mRNA vaccines [...] Read more.

Previous studies have shown that the herpes zoster subunit vaccine Shingrix™ performs well in clinical trials. However, the key ingredient in its adjuvant, QS21, is extracted from rare plants in South America, so vaccine production is limited. Compared with subunit vaccines, mRNA vaccines have the advantages of faster production and not requiring adjuvants, but currently, there is no authorized mRNA vaccine for herpes zoster. Therefore, this study focused on herpes zoster subunit and mRNA vaccines. We prepared a herpes zoster mRNA vaccine and compared the effects of vaccine type, immunization route, and adjuvant use on vaccine immunological efficacy. The mRNA vaccine was injected directly into mice via subcutaneous or intramuscular injection. The subunit vaccine was mixed with adjuvants before immunization. The adjuvants include B2Q or alum. B2Q is BW006S + 2395S + QS21. BW006S and 2395S are phosphodiester CpG oligodeoxynucleotides (CpG ODNs). Then, we compared the cell-mediated immunity (CIM) and humoral immunity levels of the different groups of mice. The results showed that the immune responses of mice inoculated with the mRNA vaccine prepared in this study were not significantly different from those of mice inoculated with the protein subunit vaccine supplemented with the B2Q. The mRNA vaccine-induced immune responses following subcutaneous or intramuscular injection, and the different immunization routes did not lead to significant differences in immune response intensity. Similar results were also observed for the protein subunit vaccine adjuvanted with B2Q but not alum. The above results suggest that our experiment can provide a reference for the preparation of mRNA vaccines against herpes zoster and has certain reference significance for the selection of the immunization route; that is, there is no significant difference in the immune response caused by subcutaneous versus an intramuscular injection, so the injection route can be determined according to the actual situation of individuals. Full article

(This article belongs to the Special Issue Cellular Immune Responses to Infectious Diseases)

► Show Figures

Figure 1

13 pages, 1334 KiB

Open AccessEditor’s ChoiceArticle

Predicted Public Health and Economic Impact of Respiratory Syncytial Virus Vaccination with Variable Duration of Protection for Adults ≥60 Years in Belgium

by Maarten J. Postma, Chih-Yuan Cheng, Nasuh C. Buyukkaramikli, Luis Hernandez Pastor, Ine Vandersmissen, Thierry Van Effelterre, Peter Openshaw and Steven Simoens

Vaccines 2023, 11(5), 990; https://doi.org/10.3390/vaccines11050990 - 16 May 2023

Cited by 7 | Viewed by 4944

Abstract

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection (ARI) in older adults. This study used a static, cohort-based decision-tree model to estimate the public health and economic impact of vaccination against RSV in Belgians aged ≥60 years compared with [...] Read more.

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection (ARI) in older adults. This study used a static, cohort-based decision-tree model to estimate the public health and economic impact of vaccination against RSV in Belgians aged ≥60 years compared with no vaccination for different vaccine duration of protection profiles from a healthcare payer perspective. Three vaccine protection durations were compared (1, 3, and 5 years), and several sensitivity and scenario analyses were performed. Results showed that an RSV vaccine with a 3-year duration of protection would prevent 154,728 symptomatic RSV-ARI cases, 3688 hospitalizations, and 502 deaths over three years compared to no vaccination in older adults and would save EUR 35,982,857 in direct medical costs in Belgium. The number needed to vaccinate to prevent one RSV-ARI case was 11 for the 3-year duration profile, while it was 28 and 8 for the 1- and 5-year vaccine duration profiles, respectively. The model was generally robust in sensitivity analyses varying key input values. This study suggested that vaccination could substantially decrease the public health and economic burden of RSV in adults ≥60 years in Belgium, with benefits increasing with a longer duration of vaccine protection. Full article

(This article belongs to the Section Human Vaccines and Public Health)

► Show Figures

Figure 1

12 pages, 1507 KiB

Open AccessEditor’s ChoiceArticle

Validation of an HPLC-CAD Method for Determination of Lipid Content in LNP-Encapsulated COVID-19 mRNA Vaccines

by Xiaojuan Yu, Chuanfei Yu, Xiaohong Wu, Yu Cui, Xiaoda Liu, Yan Jin, Yuhua Li and Lan Wang

Vaccines 2023, 11(5), 937; https://doi.org/10.3390/vaccines11050937 - 4 May 2023

Cited by 11 | Viewed by 8300

Abstract

Lipid nanoparticles (LNPs) are widely used as delivery systems for mRNA vaccines. The stability and bilayer fluidity of LNPs are determined by the properties and contents of the various lipids used in the formulation system, and the delivery efficiency of LNPs largely depends [...] Read more.

Lipid nanoparticles (LNPs) are widely used as delivery systems for mRNA vaccines. The stability and bilayer fluidity of LNPs are determined by the properties and contents of the various lipids used in the formulation system, and the delivery efficiency of LNPs largely depends on the lipid composition. For the quality control of such vaccines, here we developed and validated an HPLC-CAD method to identify and determine the contents of four lipids in an LNP-encapsulated COVID-19 mRNA vaccine to support lipid analysis for the development of new drugs and vaccines. Full article

(This article belongs to the Special Issue Vaccines or Immunotherapy for Viruses)

► Show Figures

Figure 1

28 pages, 1360 KiB

Open AccessEditor’s ChoiceReview

Engineered Phage-Based Cancer Vaccines: Current Advances and Future Directions

by Murali Ragothaman and So Young Yoo

Vaccines 2023, 11(5), 919; https://doi.org/10.3390/vaccines11050919 - 29 Apr 2023

Cited by 22 | Viewed by 7047

Abstract

Bacteriophages have emerged as versatile tools in the field of bioengineering, with enormous potential in tissue engineering, vaccine development, and immunotherapy. The genetic makeup of phages can be harnessed for the development of novel DNA vaccines and antigen display systems, as they can [...] Read more.

Bacteriophages have emerged as versatile tools in the field of bioengineering, with enormous potential in tissue engineering, vaccine development, and immunotherapy. The genetic makeup of phages can be harnessed for the development of novel DNA vaccines and antigen display systems, as they can provide a highly organized and repetitive presentation of antigens to immune cells. Bacteriophages have opened new possibilities for the targeting of specific molecular determinants of cancer cells. Phages can be used as anticancer agents and carriers of imaging molecules and therapeutics. In this review, we explored the role of bacteriophages and bacteriophage engineering in targeted cancer therapy. The question of how the engineered bacteriophages can interact with the biological and immunological systems is emphasized to comprehend the underlying mechanism of phage use in cancer immunotherapy. The effectiveness of phage display technology in identifying high-affinity ligands for substrates, such as cancer cells and tumor-associated molecules, and the emerging field of phage engineering and its potential in the development of effective cancer treatments are discussed. We also highlight phage usage in clinical trials as well as the related patents. This review provides a new insight into engineered phage-based cancer vaccines. Full article

(This article belongs to the Section Cancer Vaccines and Immunotherapy)

► Show Figures

Figure 1

19 pages, 883 KiB

Open AccessEditor’s ChoiceReview

T Cell Based Immunotherapy for Cancer: Approaches and Strategies

by Muzamil Y. Want, Zeenat Bashir and Rauf A. Najar

Vaccines 2023, 11(4), 835; https://doi.org/10.3390/vaccines11040835 - 13 Apr 2023

Cited by 31 | Viewed by 5289

Abstract

T cells are critical in destroying cancer cells by recognizing antigens presented by MHC molecules on cancer cells or antigen-presenting cells. Identifying and targeting cancer-specific or overexpressed self-antigens is essential for redirecting T cells against tumors, leading to tumor regression. This is achieved [...] Read more.

T cells are critical in destroying cancer cells by recognizing antigens presented by MHC molecules on cancer cells or antigen-presenting cells. Identifying and targeting cancer-specific or overexpressed self-antigens is essential for redirecting T cells against tumors, leading to tumor regression. This is achieved through the identification of mutated or overexpressed self-proteins in cancer cells, which guide the recognition of cancer cells by T-cell receptors. There are two main approaches to T cell-based immunotherapy: HLA-restricted and HLA-non-restricted Immunotherapy. Significant progress has been made in T cell-based immunotherapy over the past decade, using naturally occurring or genetically engineered T cells to target cancer antigens in hematological malignancies and solid tumors. However, limited specificity, longevity, and toxicity have limited success rates. This review provides an overview of T cells as a therapeutic tool for cancer, highlighting the advantages and future strategies for developing effective T cell cancer immunotherapy. The challenges associated with identifying T cells and their corresponding antigens, such as their low frequency, are also discussed. The review further examines the current state of T cell-based immunotherapy and potential future strategies, such as the use of combination therapy and the optimization of T cell properties, to overcome current limitations and improve clinical outcomes. Full article

(This article belongs to the Special Issue Immunology and Immunotherapy in Cancer)

► Show Figures

Figure 1

13 pages, 1389 KiB

Open AccessEditor’s ChoiceArticle

Third BNT162b2 mRNA SARS-CoV-2 Vaccine Dose Significantly Enhances Immunogenicity in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation

by Israel Henig, Jonathan Isenberg, Dana Yehudai-Ofir, Ronit Leiba, Shimrit Ringelstein-Harlev, Ron Ram, Batia Avni, Odelia Amit, Sigal Grisariu, Tehila Azoulay, Ilana Slouzkey and Tsila Zuckerman

Vaccines 2023, 11(4), 775; https://doi.org/10.3390/vaccines11040775 - 31 Mar 2023

Cited by 5 | Viewed by 3373

Abstract

COVID-19-related mortality among hematopoietic stem cell transplantation (HSCT) recipients in the pre-vaccine era ranged between 22 and 33%. The Pfizer/BioNTech BNT162b2 vaccine demonstrated significant immunogenicity and efficacy in the healthy population; however, its long-term effects on allogeneic HSCT recipients remained unclear. Our study [...] Read more.

COVID-19-related mortality among hematopoietic stem cell transplantation (HSCT) recipients in the pre-vaccine era ranged between 22 and 33%. The Pfizer/BioNTech BNT162b2 vaccine demonstrated significant immunogenicity and efficacy in the healthy population; however, its long-term effects on allogeneic HSCT recipients remained unclear. Our study longitudinally evaluated humoral and cellular responses to the BNT162b2 vaccine in adult allogeneic HSCT patients. A positive response was defined as antibody titers ≥ 150 AU/mL post-second vaccination. Among 77 included patients, 51 (66.2%) responded to vaccination. Response-associated factors were female gender, recent anti-CD20 therapy, and a longer interval between transplant and vaccination. Response rates reached 83.7% in patients vaccinated >12 months post-transplant. At 6 months post-second vaccination, antibody titers dropped, but were significantly increased with the booster dose. Moreover, 43% (6/14) of non-responders to the second vaccination acquired sufficient antibody titers after booster administration, resulting in an overall response rate of 79.5% for the entire cohort. The BNT162b2 vaccine was effective in allogeneic transplant recipients. Although antibody titers decreased with time, the third vaccination led to their significant elevation, with 93% of third-dose responders maintaining titers above 150 AU/mL at 3 months post-administration. Full article

(This article belongs to the Special Issue Safety and Immunogenicity of the COVID-19 Vaccine)

► Show Figures

Figure 1

26 pages, 749 KiB

Open AccessEditor’s ChoiceReview

Anti-HERV-K Drugs and Vaccines, Possible Therapies against Tumors

by Sepideh Hosseiniporgham and Leonardo Antonio Sechi

Vaccines 2023, 11(4), 751; https://doi.org/10.3390/vaccines11040751 - 28 Mar 2023

Cited by 9 | Viewed by 5375

Abstract

The footprint of human endogenous retroviruses (HERV), specifically HERV-K, has been found in malignancies, such as melanoma, teratocarcinoma, osteosarcoma, breast cancer, lymphoma, and ovary and prostate cancers. HERV-K is characterized as the most biologically active HERV due to possession of open reading frames [...] Read more.

The footprint of human endogenous retroviruses (HERV), specifically HERV-K, has been found in malignancies, such as melanoma, teratocarcinoma, osteosarcoma, breast cancer, lymphoma, and ovary and prostate cancers. HERV-K is characterized as the most biologically active HERV due to possession of open reading frames (ORF) for all Gag, Pol, and Env genes, which enables it to be more infective and obstructive towards specific cell lines and other exogenous viruses, respectively. Some factors might contribute to carcinogenicity and at least one of them has been recognized in various tumors, including overexpression/methylation of long interspersed nuclear element 1 (LINE-1), HERV-K Gag, and Env genes themselves plus their transcripts and protein products, and HERV-K reverse transcriptase (RT). Therapies effective for HERV-K-associated tumors mostly target invasive autoimmune responses or growth of tumors through suppression of HERV-K Gag or Env protein and RT. To design new therapeutic options, more studies are needed to better understand whether HERV-K and its products (Gag/Env transcripts and HERV-K proteins/RT) are the initiators of tumor formation or just the disorder’s developers. Accordingly, this review aims to present evidence that highlights the association between HERV-K and tumorigenicity and introduces some of the available or potential therapies against HERV-K-induced tumors. Full article

(This article belongs to the Special Issue State of the Art and Future Directions of Synthetic Biology-Armed Vaccine Development)

► Show Figures

Figure 1

17 pages, 4655 KiB

Open AccessEditor’s ChoiceArticle

Heterologous Vector—mRNA Based SARS-CoV-2 Vaccination Strategy Appears Superior to a Homologous Vector—Based Vaccination Scheme in German Healthcare Workers Regarding Humoral SARS-CoV-2 Response Indicating a High Boosting Effect by mRNA Vaccines

by Catharina Gerhards, Margot Thiaucourt, Michael Hetjens, Verena Haselmann, Michael Neumaier and Maximilian Kittel

Vaccines 2023, 11(3), 701; https://doi.org/10.3390/vaccines11030701 - 19 Mar 2023

Cited by 6 | Viewed by 3221

Abstract

Background: Longitudinal humoral SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) immunity for up to 15 months due to vaccination, the efficacy of vaccination strategies (homologous, vector–vector versus heterologous, vector–mRNA), the influence of vaccination side effects, and the infection rate in German healthcare [...] Read more.

Background: Longitudinal humoral SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) immunity for up to 15 months due to vaccination, the efficacy of vaccination strategies (homologous, vector–vector versus heterologous, vector–mRNA), the influence of vaccination side effects, and the infection rate in German healthcare workers need to be investigated. Methods: In this study, 103 individuals vaccinated against SARS-CoV-2 were enrolled to examine their anti-SARS-CoV-2 anti-N- and anti-RBD/S1-Ig levels. A total of 415 blood samples in lithium heparin tubes were prospectively obtained, and a structured survey regarding medical history, type of vaccine, and vaccination reactions was conducted. Results: All participants demonstrated a humoral immune response, among whom no values decreased below the positivity cutoff. Five to six months after the third vaccination, three participants showed anti-RBD/S1 antibodies of less than 1000 U/mL. We observed higher levels for heterologous mRNA-/vector-based combinations compared to pure vector-based vaccination after the second vaccination, which is harmonized after a third vaccination with the mRNA-vaccine only in both cohorts. The incidence of vaccine breakthrough in a highly exposed cohort was 60.3%. Conclusion: Sustained long-term humoral immunity was observed, indicating the superiority of a heterologous mRNA-/vector-based combination compared to pure vector-based vaccination. There was longevity of anti-RBD/S1 antibodies of at least 4 and up to 7 months without external stimulus. Regarding vaccination reactogenity, the occurrence of local symptoms as pain at the injection site was increased after the first mRNA application compared to the vector–vector cohort with a general decrease in adverse events at later vaccination time points. Overall, a correlation between the humoral vaccination response and vaccination side effects was not observed. Despite the high prevalence of vaccine breakthroughs, these only occurred in the later course of the study when more infectious variants, which are, however, associated with milder courses, were present. These results provide insights into vaccine-related serologic responses, and the study should be expanded using additional vaccine doses and novel variants in the future. Full article

(This article belongs to the Special Issue Detection of SARS-CoV-2 Neutralizing Antibodies and Vaccine Development)

► Show Figures

Figure 1

15 pages, 1150 KiB

Open AccessEditor’s ChoiceReview

The Impact of COVID-19 on Pediatric Malignancy Diagnosis and Treatment: Never the Same but Lessons Learned

by Ghadir K. Katato, Prasiksha Sitaula, Avanti Gupte and Eman T. Al-Antary

Vaccines 2023, 11(3), 667; https://doi.org/10.3390/vaccines11030667 - 15 Mar 2023

Cited by 7 | Viewed by 2927

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic affected the pediatric oncology population globally. Over the course of 2 years, increasing reports have been made to better understand this entity and its pathologic complications on these patients. The pandemic has allowed healthcare [...] Read more.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic affected the pediatric oncology population globally. Over the course of 2 years, increasing reports have been made to better understand this entity and its pathologic complications on these patients. The pandemic has allowed healthcare providers, hospital systems, and leading oncologic societies to quickly adapt and formulate new guidelines for the effective understanding, management, and treatment of patients with pediatric malignancy. Full article

(This article belongs to the Special Issue Oncology in the Era of SARS-CoV-2)

► Show Figures

Figure 1

11 pages, 522 KiB

Open AccessEditor’s ChoiceCommunication

Evolution and Progress of mRNA Vaccines in the Treatment of Melanoma: Future Prospects

by Dimitrios Bafaloukos, Ioanna Gazouli, Christos Koutserimpas and George Samonis

Vaccines 2023, 11(3), 636; https://doi.org/10.3390/vaccines11030636 - 13 Mar 2023

Cited by 30 | Viewed by 6515

Abstract

mRNA vaccines encoding tumor antigens may be able to sensitize the immune system of the host against cancer cells, enhancing antigen presentation and immune response. Since the breakout of the COVID19 pandemic, interest in mRNA vaccines has been accelerating, as vaccination against the [...] Read more.

mRNA vaccines encoding tumor antigens may be able to sensitize the immune system of the host against cancer cells, enhancing antigen presentation and immune response. Since the breakout of the COVID19 pandemic, interest in mRNA vaccines has been accelerating, as vaccination against the virus served as a measure to limit disease spread. Given that immunotherapy has been the cornerstone of melanoma treatment over the last several decades, further innate immunity enhancement by targeted mRNA vaccines could be the next pivotal achievement in melanoma treatment. Preclinical data coming from murine cancer models have already provided evidence of mRNA vaccines’ ability to induce host immune responses against cancer. Moreover, specific immune responses have been observed in melanoma patients receiving mRNA vaccines, while the recent KEYNOTE-942 trial may establish the incorporation of the mRNA-4157/V940 vaccine into the melanoma treatment algorithm, in combination with immune checkpoint inhibition. As the existing data are further tested and reviewed, investigators are already gaining enthusiasm about this novel, promising pathway in cancer therapy. Full article

(This article belongs to the Special Issue Oncology in the Era of SARS-CoV-2)

► Show Figures

Figure 1

15 pages, 9874 KiB

Open AccessEditor’s ChoiceArticle

Phosphatidylserine-Exposing Annexin A1-Positive Extracellular Vesicles: Potential Cancer Biomarkers

by Gloria I. Perez, Matthew P. Bernard, Daniel Vocelle, Ahmed A. Zarea, Najla A. Saleh, Matthew A. Gagea, Doug Schneider, Maxine Bauzon, Terry Hermiston and Masamitsu Kanada

Vaccines 2023, 11(3), 639; https://doi.org/10.3390/vaccines11030639 - 13 Mar 2023

Cited by 12 | Viewed by 3383

Abstract

Under physiological conditions, phosphatidylserine (PS) predominantly localizes to the cytosolic leaflet of the plasma membrane of cells. During apoptosis, PS is exposed on the cell surface and serves as an “eat-me” signal for macrophages to prevent releasing self-immunogenic cellular components from dying cells [...] Read more.

Under physiological conditions, phosphatidylserine (PS) predominantly localizes to the cytosolic leaflet of the plasma membrane of cells. During apoptosis, PS is exposed on the cell surface and serves as an “eat-me” signal for macrophages to prevent releasing self-immunogenic cellular components from dying cells which could potentially lead to autoimmunity. However, increasing evidence indicates that viable cells can also expose PS on their surface. Interestingly, tumor cell-derived extracellular vesicles (EVs) externalize PS. Recent studies have proposed PS-exposing EVs as a potential biomarker for the early detection of cancer and other diseases. However, there are confounding results regarding subtypes of PS-positive EVs, and knowledge of PS exposure on the EV surface requires further elucidation. In this study, we enriched small EVs (sEVs) and medium/large EVs (m/lEVs) from conditioned media of breast cancer cells (MDA-MB-231, MDA-MB-468) and non-cancerous cells (keratinocytes, fibroblasts). Since several PS-binding molecules are available to date, we compared recombinant proteins of annexin A5 and the carboxylated glutamic acid domain of Protein S (GlaS), also specific for PS, to detect PS-exposing EVs. Firstly, PS externalization in each EV fraction was analyzed using a bead-based EV assay, which combines EV capture using microbeads and analysis of PS-exposing EVs by flow cytometry. The bulk EV assay showed higher PS externalization in m/lEVs derived from MDA-MB-468 cells but not from MDA-MB-231 cells, while higher binding of GlaS was also observed in m/lEVs from fibroblasts. Second, using single EV flow cytometry, PS externalization was also analyzed on individual sEVs and m/lEVs. Significantly higher PS externalization was detected in m/lEVs (annexin A1⁺) derived from cancer cells compared to m/lEVs (annexin A1⁺) from non-cancerous cells. These results emphasize the significance of PS-exposing m/lEVs (annexin A1⁺) as an undervalued EV subtype for early cancer detection and provide a better understanding of PS externalization in disease-associated EV subtypes. Full article

(This article belongs to the Special Issue Extracellular Vesicles: A New Mechanism of Intercellular Communication for Immune Regulation in Cancer, Autoimmune Diseases, and Infectious Diseases)

► Show Figures

Figure 1

13 pages, 1257 KiB

Open AccessEditor’s ChoiceArticle

Survivin (BIRC5) Peptide Vaccine in the 4T1 Murine Mammary Tumor Model: A Potential Neoadjuvant T Cell Immunotherapy for Triple Negative Breast Cancer: A Preliminary Study

by Scott R. Burkholz, Charles V. Herst, Richard T. Carback, Paul E. Harris and Reid M. Rubsamen

Vaccines 2023, 11(3), 644; https://doi.org/10.3390/vaccines11030644 - 13 Mar 2023

Cited by 12 | Viewed by 4759

Abstract

A triple negative breast cancer model using the murine 4T1 tumor cell line was used to explore the efficacy of an adjuvanted survivin peptide microparticle vaccine using tumor growth as the outcome metric. We first performed tumor cell dose titration studies to determine [...] Read more.

A triple negative breast cancer model using the murine 4T1 tumor cell line was used to explore the efficacy of an adjuvanted survivin peptide microparticle vaccine using tumor growth as the outcome metric. We first performed tumor cell dose titration studies to determine a tumor cell dose that resulted in sufficient tumor takes but allowed multiple serial measurements of tumor volumes, yet with minimal morbidity/mortality within the study period. Later, in a second cohort of mice, the survivin peptide microparticle vaccine was administered via intraperitoneal injection at the study start with a second dose given 14 days later. An orthotopic injection of 4T1 cells into the mammary tissue was performed on the same day as the administration of the second vaccine dose. The mice were followed for up to 41 days with subcutaneous measurements of tumor volume made every 3–4 days. Vaccination with survivin peptides was associated with a peptide antigen-specific gamma interferon enzyme-linked immunosorbent spot response in the murine splenocyte population but was absent from the control microparticle group. At the end of the study, we found that vaccination with adjuvanted survivin peptide microparticles resulted in statistically significant slower primary tumor growth rates in BALB/c mice challenged with 4T1 cells relative to the control peptideless vaccination group. These studies suggest that T cell immunotherapy specifically targeting survivin might be an applicable neoadjuvant immunotherapy therapy for triple negative breast cancer. More preclinical studies and clinical trials are needed to explore this concept further. Full article

(This article belongs to the Special Issue Advances in Cancer Immunotherapy and Vaccines Research)

► Show Figures

Figure 1

13 pages, 1306 KiB

Open AccessEditor’s ChoiceArticle

Not All Conservatives Are Vaccine Hesitant: Examining the Influence of Misinformation Exposure, Political Ideology, and Flu Vaccine Acceptance on COVID-19 Vaccine Hesitancy

by Muhammad Ehab Rasul and Saifuddin Ahmed

Vaccines 2023, 11(3), 586; https://doi.org/10.3390/vaccines11030586 - 3 Mar 2023

Cited by 9 | Viewed by 4700

Abstract

Despite the mass availability of COVID-19 vaccines in the United States, many Americans are still reluctant to take a vaccine as an outcome from exposure to misinformation. Additionally, while scholars have paid attention to COVID-19 vaccine hesitancy, the influence of general vaccine hesitancy [...] Read more.

Despite the mass availability of COVID-19 vaccines in the United States, many Americans are still reluctant to take a vaccine as an outcome from exposure to misinformation. Additionally, while scholars have paid attention to COVID-19 vaccine hesitancy, the influence of general vaccine hesitancy for important viruses such as the flu has largely been ignored. Using nationally representative data from Pew Research Center’s American Trends Panel survey (Wave 79), this study examined the relationship between perceived misinformation exposure, COVID-19 vaccine hesitancy, flu vaccine acceptance, political ideology, and demographic trends. The findings suggest that those who accepted the flu vaccine were less likely to be COVID-19 vaccine-hesitant. In addition, moderation analyses showed that perceived misinformation exposure increases COVID-19 vaccine hesitancy for conservatives and moderates but not for liberals. However, perceived misinformation exposure influences COVID-19 vaccine hesitancy among conservatives only if they are also flu vaccine-hesitant. Perceived misinformation exposure has no role in COVID-19 vaccine hesitancy if individuals (irrespective of political ideology) are regular with their flu vaccine. The results suggest that the effect of misinformation exposure on negative attitudes toward COVID-19 may be associated with generalized vaccine hesitancy (e.g., flu). The practical and theoretical implications are discussed. Full article

(This article belongs to the Special Issue Recent Advances in Factors Associated with Vaccine Hesitancy and Acceptance)

► Show Figures

Figure 1

16 pages, 720 KiB

Open AccessEditor’s ChoiceArticle

Qualitative Insights into Vaccine Uptake of Nursing Staff in Long-Term Care Facilities in Finland

by Anna-Leena Lohiniva, Idil Hussein, Jaana-Marija Lehtinen, Jonas Sivelä, Suvi Hyökki, Hanna Nohynek, Pekka Nuorti and Outi Lyytikäinen

Vaccines 2023, 11(3), 530; https://doi.org/10.3390/vaccines11030530 - 23 Feb 2023

Cited by 6 | Viewed by 3736

Abstract

Vaccine hesitancy and refusal have undermined COVID-19 vaccination efforts of nursing staff. This study aimed to identify behavioral factors associated with COVID-19 vaccine uptake among unvaccinated nursing staff in long-term care facilities (LTCF) in Finland. Methodology: The study was based on the Theoretical [...] Read more.

Vaccine hesitancy and refusal have undermined COVID-19 vaccination efforts of nursing staff. This study aimed to identify behavioral factors associated with COVID-19 vaccine uptake among unvaccinated nursing staff in long-term care facilities (LTCF) in Finland. Methodology: The study was based on the Theoretical Domains Framework. Data were collected through qualitative in-depth interviews among nursing staff and managers of LTCFs. The analysis was based on thematic analysis. We identified seven behavioral domains, with several themes, that reduced the staff’s intention to get vaccinated: knowledge (information overload, inability to identify trustworthy information sources, lack of vaccine-specific and understandable scientific information), beliefs about consequences (incorrect perceptions about the vaccine effectiveness, and lack of trust in the safety of the vaccine), social influences (influence of family and friends), reinforcement (limited abilities of the management to encourage vaccination), beliefs about capabilities (pregnancy or desire to get pregnant), psychological factors (coping with changing opinion), and emotions (confusion, suspicion, disappointment, and fatigue). We also identified three behavioral domains that encouraged vaccine uptake: social influences (trust in health authorities), environmental context and resources (vaccination logistics), and work and professional role (professional pride). The study findings can help authorities to develop tailored vaccine promotion strategies for healthcare workers in LTCFs. Full article

(This article belongs to the Special Issue Vaccination Hesitancy across the Globe)

► Show Figures

Figure 1

13 pages, 434 KiB

Open AccessEditor’s ChoiceArticle

Development of Autoantibodies Following BNT162b2 mRNA COVID-19 Vaccination and Their Association with Disease Flares in Adult Patients with Autoimmune Inflammatory Rheumatic Diseases (AIIRD) and the General Population: Results of 1-Year Prospective Follow-Up Study

by Tal Gazitt, Tali Eviatar, Jacqueline Shear, Roni Meidan, Victoria Furer, Joy Feld, Amir Haddad, Muna Elias, Nizar Hijazi, Nili Stein, Pninit Shaked Mishan, Anna Zetser, Hagit Peleg, Ori Elkayam and Devy Zisman

Vaccines 2023, 11(2), 476; https://doi.org/10.3390/vaccines11020476 - 17 Feb 2023

Cited by 11 | Viewed by 3890

Abstract

Development of autoantibodies following BNT162b2 mRNA COVID-19 vaccination and their association with disease flares in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and the general population: results of 1-year prospective follow-up study. We conducted a prospective study aimed at investigating the incidence [...] Read more.

Development of autoantibodies following BNT162b2 mRNA COVID-19 vaccination and their association with disease flares in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and the general population: results of 1-year prospective follow-up study. We conducted a prospective study aimed at investigating the incidence of appearance of autoantibodies (antinuclear, antiphospholipid, and rheumatoid factor) in the sera of 463 adult patients with AIIRD compared to 55 controls from the general population prior to, and following the second and third vaccine doses, and at 1-year of follow-up. Pre- and post-vaccination disease activity indices and the association of autoantibodies with rheumatic disease flares and new onset AIIRD were examined. Autoantibody development of any type in AIIRD patients vs. the controls was 4.0% (vs. 6.7%, p = 0.423) following two vaccine doses and 7.6% (vs. 0%, p = 0.152) after three doses. There was no significant difference in sex, age, or disease-type among individuals with and without autoantibody development, regardless of the immunosuppressant use. More patients developed autoantibodies following the third than the second vaccine dose (p = 0.004). Disease flares occurred in 5.8% and 7.2% of AIIRD patients following second and third vaccine doses, respectively, with autoantibody production increasing the risk of flares following the second (p = 0.002) and third (p = 0.004) vaccine doses. BNT162b2 vaccination resulted in the development of autoantibodies in a minority of AIIRD patients and controls. Autoantibody development was associated with disease flares in patients, but no new-onset autoimmunity was observed. Full article

(This article belongs to the Special Issue Antibody Response of Vaccines to SARS-CoV-2)

21 pages, 5788 KiB

Open AccessEditor’s ChoiceArticle

Toxicological Assessments of a Pandemic COVID-19 Vaccine—Demonstrating the Suitability of a Platform Approach for mRNA Vaccines

by Cynthia M. Rohde, Claudia Lindemann, Michael Giovanelli, Rani S. Sellers, Jan Diekmann, Shambhunath Choudhary, Lila Ramaiah, Annette B. Vogel, Yana Chervona, Alexander Muik and Ugur Sahin

Vaccines 2023, 11(2), 417; https://doi.org/10.3390/vaccines11020417 - 11 Feb 2023

Cited by 23 | Viewed by 7091

Abstract

The emergence of SARS-CoV-2 at the end of 2019 required the swift development of a vaccine to address the pandemic. Nonclinical GLP-compliant studies in Wistar Han rats were initiated to assess the local tolerance, systemic toxicity, and immune response to four mRNA vaccine [...] Read more.

The emergence of SARS-CoV-2 at the end of 2019 required the swift development of a vaccine to address the pandemic. Nonclinical GLP-compliant studies in Wistar Han rats were initiated to assess the local tolerance, systemic toxicity, and immune response to four mRNA vaccine candidates encoding immunogens derived from the spike (S) glycoprotein of SARS-CoV-2, encapsulated in lipid nanoparticles (LNPs). Vaccine candidates were administered intramuscularly once weekly for three doses at 30 and/or 100 µg followed by a 3-week recovery period. Clinical pathology findings included higher white blood cell counts and acute phase reactant concentrations, lower platelet and reticulocyte counts, and lower RBC parameters. Microscopically, there was increased cellularity (lymphocytes) in the lymph nodes and spleen, increased hematopoiesis in the bone marrow and spleen, acute inflammation and edema at the injection site, and minimal hepatocellular vacuolation. These findings were generally attributed to the anticipated immune and inflammatory responses to the vaccines, except for hepatocyte vacuolation, which was interpreted to reflect hepatocyte LNP lipid uptake, was similar between candidates and resolved or partially recovered at the end of the recovery phase. These studies demonstrated safety and tolerability in rats, supporting SARS-CoV-2 mRNA-LNP vaccine clinical development. Full article

(This article belongs to the Special Issue COVID-19 Vaccine Candidate Development)

► Show Figures

Figure 1

8 pages, 249 KiB

Open AccessEditor’s ChoiceArticle

Association between COVID-19 and Seasonal Influenza Vaccines to Vaccine Hesitancy, Intolerance of Uncertainty and Mental Health

by Maayan Shacham, Yaira Hamama-Raz, Menachem Ben-Ezra and Yafit Levin

Vaccines 2023, 11(2), 403; https://doi.org/10.3390/vaccines11020403 - 9 Feb 2023

Cited by 7 | Viewed by 3113

Abstract

Vaccine hesitancy is a universal problem that is becoming more prevalent, ranging from partial acceptance to the complete refusal of various vaccines. The current study seeks to assess the relationship between vaccine hesitancy, intolerance of uncertainty, and mental health factors and those who [...] Read more.

Vaccine hesitancy is a universal problem that is becoming more prevalent, ranging from partial acceptance to the complete refusal of various vaccines. The current study seeks to assess the relationship between vaccine hesitancy, intolerance of uncertainty, and mental health factors and those who were vaccinated against COVID-19 and seasonal influenza in comparison to those who did not vaccinate against both or decided to be vaccinated with only one of these vaccines. Employing a cross-sectional design, 1068 Israeli participants were recruited via social media (mainly Facebook) and Whatsapp and completed questionnaires assessing vaccine hesitancy, intolerance of uncertainty, and mental health factors. Our results revealed that previous history of neither COVID-19 nor seasonal influenza vaccination was associated with increased vaccine hesitancy. In addition, individuals who received either one vaccine or both claimed elevated levels of intolerance of uncertainty and reported elevated levels of mental health symptoms. Therefore, an association between vaccine hesitancy and intolerance of uncertainty and mental health symptoms is demonstrated. Future campaigns against vaccine hesitancy may focus on the intolerance of uncertainty in vaccine-hesitant individuals. Full article

(This article belongs to the Special Issue Vaccines Hesitancy and Public Health)

12 pages, 286 KiB

Open AccessEditor’s ChoiceArticle

Predictors of Seasonal Influenza Vaccination Willingness among High-Risk Populations Three Years after the Onset of the COVID-19 Pandemic

by Aglaia Katsiroumpa, Panayota Sourtzi, Daphne Kaitelidou, Olga Siskou, Olympia Konstantakopoulou and Petros Galanis

Vaccines 2023, 11(2), 331; https://doi.org/10.3390/vaccines11020331 - 1 Feb 2023

Cited by 13 | Viewed by 3664

Abstract

High-risk populations are at increased risk of severe influenza-related illness, hospitalization, and death due to influenza. The aim of our study was to assess the willingness of high-risk populations to take the influenza vaccine for the 2022–2023 season, and to investigate the factors [...] Read more.

High-risk populations are at increased risk of severe influenza-related illness, hospitalization, and death due to influenza. The aim of our study was to assess the willingness of high-risk populations to take the influenza vaccine for the 2022–2023 season, and to investigate the factors associated with such willingness. We conducted a cross-sectional study in Greece in September 2022 using a convenience sample. We considered demographic characteristics, COVID-19-related variables, resilience, social support, anxiety, depression, and COVID-19-related burnout as potential predictors. Among participants, 39.4% were willing to accept the seasonal influenza vaccine, 33.9% were unwilling, and 26.8% were hesitant. Multivariable analysis identified that increased age and increased family support were associated with increased influenza vaccination willingness. Moreover, participants that have received COVID-19 booster doses were more willing to accept the influenza vaccine. In contrast, adverse effects because of COVID-19 vaccination and exhaustion due to measures against COVID-19 reduced influenza vaccination willingness. We found that the intention of high-risk populations to receive the influenza vaccine was low. Our study contributes to an increased understanding of the factors that affect vaccination willingness. Public health authorities could use this information to update vaccination programs against influenza. Emphasis should be given on safety and effectiveness issues. Full article

(This article belongs to the Special Issue Vaccines Hesitancy and Public Health)

18 pages, 2921 KiB

Open AccessEditor’s ChoiceArticle

Assessment of Immunogenicity and Efficacy of CV0501 mRNA-Based Omicron COVID-19 Vaccination in Small Animal Models

by Nicole Roth, Janina Gergen, Kristina Kovacikova, Stefan O. Mueller, Lorenz Ulrich, Jacob Schön, Nico Joel Halwe, Charlie Fricke, Björn Corleis, Anca Dorhoi, Donata Hoffmann, Martin Beer, Domenico Maione, Benjamin Petsch and Susanne Rauch

Vaccines 2023, 11(2), 318; https://doi.org/10.3390/vaccines11020318 - 31 Jan 2023

Cited by 6 | Viewed by 4206

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron and its subvariants (BA.2, BA.4, BA.5) represented the most commonly circulating variants of concern (VOC) in the coronavirus disease 2019 (COVID-19) pandemic in 2022. Despite high vaccination rates with approved SARS-CoV-2 vaccines encoding the ancestral spike [...] Read more.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron and its subvariants (BA.2, BA.4, BA.5) represented the most commonly circulating variants of concern (VOC) in the coronavirus disease 2019 (COVID-19) pandemic in 2022. Despite high vaccination rates with approved SARS-CoV-2 vaccines encoding the ancestral spike (S) protein, these Omicron subvariants have collectively resulted in increased viral transmission and disease incidence. This necessitates the development and characterization of vaccines incorporating later emerging S proteins to enhance protection against VOC. In this context, bivalent vaccine formulations may induce broad protection against VOC and potential future SARS-CoV-2 variants. Here, we report preclinical data for a lipid nanoparticle (LNP)-formulated RNActive^® N1-methylpseudouridine (N1mΨ) modified mRNA vaccine (CV0501) based on our second-generation SARS-CoV-2 vaccine CV2CoV, encoding the S protein of Omicron BA.1. The immunogenicity of CV0501, alone or in combination with a corresponding vaccine encoding the ancestral S protein (ancestral N1mΨ), was first measured in dose-response and booster immunization studies performed in Wistar rats. Both monovalent CV0501 and bivalent CV0501/ancestral N1mΨ immunization induced robust neutralizing antibody titers against the BA.1, BA.2 and BA.5 Omicron subvariants, in addition to other SARS-CoV-2 variants in a booster immunization study. The protective efficacy of monovalent CV0501 against live SARS-CoV-2 BA.2 infection was then assessed in hamsters. Monovalent CV0501 significantly reduced SARS-CoV-2 BA.2 viral loads in the airways, demonstrating protection induced by CV0501 vaccination. CV0501 has now advanced into human Phase 1 clinical trials (ClinicalTrials.gov Identifier: NCT05477186). Full article

(This article belongs to the Section COVID-19 Vaccines and Vaccination)

► Show Figures

Figure 1

14 pages, 1512 KiB

Open AccessEditor’s ChoiceArticle

The Combination of an mRNA Immunogen, a TLR7 Agonist and a PD1 Blocking Agent Enhances In-Vitro HIV T-Cell Immune Responses

by Lorena Usero, Lorna Leal, Carmen Elena Gómez, Laia Miralles, Elena Aurrecoechea, Ignasi Esteban, Berta Torres, Alexy Inciarte, Beatriz Perdiguero, Mariano Esteban, Felipe García and Montserrat Plana

Vaccines 2023, 11(2), 286; https://doi.org/10.3390/vaccines11020286 - 28 Jan 2023

Cited by 6 | Viewed by 3555

Abstract

The development of new strategies to achieve a functional cure for HIV remains a priority. We tested a novel HIV therapeutic vaccine using unmodified mRNA (TMEP-B) and mRNA modified by 1-methyl-3′-pseudouridylyl (TMEP-Bmod) expressing both a multiepitopic sequences from Gag, Pol, and Nef proteins, [...] Read more.

The development of new strategies to achieve a functional cure for HIV remains a priority. We tested a novel HIV therapeutic vaccine using unmodified mRNA (TMEP-B) and mRNA modified by 1-methyl-3′-pseudouridylyl (TMEP-Bmod) expressing both a multiepitopic sequences from Gag, Pol, and Nef proteins, including different CD4 and CD8 T-cell epitopes functionally associated with HIV control in transfected monocyte-derived dendritic cells (MDDCs) obtained from HIV infected patients. In vitro assays were used to test the mRNAs alone and in combination with immunomodulator agents, such as the TLR-7 agonist Vesatolimod and the PD-1 antagonist Nivolumab to try to improve HIV-specific cellular immune responses. Combining the mRNAs with the immunomodulators enhanced HIV-specific T-cell responses, together with the secretion of IFNγ, IP10, MIP-1α, and MIP-1β, which are fundamental mediators of viral control. Our data suggest that the mRNA vaccine prototypes TMEP-B and TMEP-Bmod, when combined with Vesatolimod and/or Nivolumab, could achieve functional cure for patients with HIV. Full article

(This article belongs to the Special Issue HIV Infection and Vaccination)

► Show Figures

Figure 1

14 pages, 293 KiB

Open AccessEditor’s ChoiceArticle

Risk of Repeated Adverse Effects following Booster Dose of mRNA COVID-19 Vaccine: Results from the MOSAICO Study

by Pietro Ferrara, Domenico Ponticelli, Lorenzo Losa, Claudia Romeo, Roberto Magliuolo, Andrea Vitale, Anna Zampella, Lucia Alleanza, Mario Borrelli, Beniamino Schiavone and Lorenzo Giovanni Mantovani

Vaccines 2023, 11(2), 247; https://doi.org/10.3390/vaccines11020247 - 22 Jan 2023

Cited by 10 | Viewed by 4690

Abstract

The successful deployment of safe and effective vaccines against coronavirus disease 2019 (COVID-19) has been crucial in reducing the global disease burden. Owing to the need for vaccination series over time, continuous observational studies are needed to estimate the COVID-19 vaccine response in [...] Read more.

The successful deployment of safe and effective vaccines against coronavirus disease 2019 (COVID-19) has been crucial in reducing the global disease burden. Owing to the need for vaccination series over time, continuous observational studies are needed to estimate the COVID-19 vaccine response in real-world conditions. In particular, the detection, assessment, and understanding of adverse effects following immunization (AEFI) with a COVID-19 vaccine are crucial to better address vaccination strategies. Therefore, this study aimed to investigate the risk of repeated AEFI post-administration of a booster dose of mRNA COVID-19 vaccine in a sample of healthcare workers (HCWs) in an Italian teaching hospital. The data on any local and systemic AEFI were studied in multivariate Poisson regression analyses to model the association between the incidence of each postvaccination symptom and its prior reporting after the administration of the previous doses. Overall, compared with the primary vaccination series, the majority of post-third dose AEFI were less reported. The results from multivariable models showed that the likelihood of reporting an AEFI after the third dose was higher in those who experienced the same postvaccination symptom after the second dose (all AEFI except for itch at injection site) and, although not significant for all AEFI, after the first dose. Any associations with age, gender, smoking habits, previous SARS-CoV-2 infection and other characteristics, as well as the health impact of AEFI were also assessed. Taken together, the results from this research support reframe AEFI symptoms as signals of a robust postvaccination reaction as well as of common vaccine response, and they add important data to inform booster vaccination strategies in HCWs and, extensively, in the adult population. Full article

(This article belongs to the Special Issue Research on Immune Response and Vaccines)

22 pages, 1178 KiB

Open AccessEditor’s ChoiceReview

Myeloid-Derived Suppressor Cells in Cancer and COVID-19 as Associated with Oxidative Stress

by Celia María Curieses Andrés, José Manuel Pérez de la Lastra, Celia Andrés Juan, Francisco J. Plou and Eduardo Pérez-Lebeña

Vaccines 2023, 11(2), 218; https://doi.org/10.3390/vaccines11020218 - 19 Jan 2023

Cited by 6 | Viewed by 3398

Abstract

Myeloid-derived suppressor cells MDSCs are a heterogeneous population of cells that expand beyond their physiological regulation during pathologies such as cancer, inflammation, bacterial, and viral infections. Their key feature is their remarkable ability to suppress T cell and natural killer NK cell responses. [...] Read more.

Myeloid-derived suppressor cells MDSCs are a heterogeneous population of cells that expand beyond their physiological regulation during pathologies such as cancer, inflammation, bacterial, and viral infections. Their key feature is their remarkable ability to suppress T cell and natural killer NK cell responses. Certain risk factors for severe COVID-19 disease, such as obesity and diabetes, are associated with oxidative stress. The resulting inflammation and oxidative stress can negatively impact the host. Similarly, cancer cells exhibit a sustained increase in intrinsic ROS generation that maintains the oncogenic phenotype and drives tumor progression. By disrupting endoplasmic reticulum calcium channels, intracellular ROS accumulation can disrupt protein folding and ultimately lead to proteostasis failure. In cancer and COVID-19, MDSCs consist of the same two subtypes (PMN-MSDC and M-MDSC). While the main role of polymorphonuclear MDSCs is to dampen the response of T cells and NK killer cells, they also produce reactive oxygen species ROS and reactive nitrogen species RNS. We here review the origin of MDSCs, their expansion mechanisms, and their suppressive functions in the context of cancer and COVID-19 associated with the presence of superoxide anion ^•O₂⁻ and reactive oxygen species ROS. Full article

(This article belongs to the Section Veterinary Vaccines)

► Show Figures

Figure 1

14 pages, 263 KiB

Open AccessEditor’s ChoiceArticle

Rural Americans’ COVID-19 Vaccine Perceptions and Willingness to Vaccinate against COVID-19 with Their Community Pharmacists: An Exploratory Study

by Alexis M. Koskan, Iris E. LoCoco, Casey L. Daniel and Benjamin S. Teeter

Vaccines 2023, 11(1), 171; https://doi.org/10.3390/vaccines11010171 - 13 Jan 2023

Cited by 13 | Viewed by 4441

Abstract

In early 2022 in the U.S., rural adults were the least likely to vaccinate against COVID-19 due to vaccine hesitancy and reduced healthcare access. This study explored the factors influencing rural adults’ COVID-19 vaccine perceptions and their acceptance of pharmacist-administered vaccination. We utilized [...] Read more.

In early 2022 in the U.S., rural adults were the least likely to vaccinate against COVID-19 due to vaccine hesitancy and reduced healthcare access. This study explored the factors influencing rural adults’ COVID-19 vaccine perceptions and their acceptance of pharmacist-administered vaccination. We utilized phone-based semi-structured interviews with 30 adults living in rural regions of one southwestern state and analyzed the data using a team-based thematic analysis approach. Vaccine-willing participants described knowing other people affected by the virus and their desired protection from the virus. They reported trusting scientific institutions and the government to provide safe vaccines. Vaccine-hesitant populations, however, feared that the COVID-19 vaccine development process had been rushed, compromising the safety of these newer vaccines. Although they differed in the news sources they preferred for receiving COVID-19 vaccine information, both vaccine-willing and vaccine-hesitant participants described trusting local authorities, such as healthcare providers and county government officials, to provide accurate COVID-19 vaccine information. Regarding the acceptability of pharmacist-administered COVID-19 vaccinations, all but one participant described their acceptance of this healthcare delivery approach. Future outreach should leverage rural adults’ trust in local sources, including community pharmacists, deemed more convenient access points to healthcare, when addressing vaccine hesitancy. Full article

(This article belongs to the Special Issue Recent Advances in Factors Associated with Vaccine Hesitancy and Acceptance)

11 pages, 280 KiB

Open AccessEditor’s ChoiceArticle

Seasonal Influenza Vaccine Intention among Nurses Who Have Been Fully Vaccinated against COVID-19: Evidence from Greece

by Petros Galanis, Aglaia Katsiroumpa, Irene Vraka, Olga Siskou, Olympia Konstantakopoulou, Theodoros Katsoulas and Daphne Kaitelidou

Vaccines 2023, 11(1), 159; https://doi.org/10.3390/vaccines11010159 - 11 Jan 2023

Cited by 10 | Viewed by 3581

Abstract

Seasonal influenza continues to be a significant public health issue causing hundreds of thousands of deaths annually. Nurses are a priority risk group for influenza vaccination and a high vaccine uptake rate among them is crucial to protect public health. Thus, the aim [...] Read more.

Seasonal influenza continues to be a significant public health issue causing hundreds of thousands of deaths annually. Nurses are a priority risk group for influenza vaccination and a high vaccine uptake rate among them is crucial to protect public health. Thus, the aim of our study was to estimate the levels of influenza vaccine acceptance, as well as its determinants, among nurses for the 2022/2023 season. We conducted a cross-sectional study with a convenience sample in Greece. We collected data via an online survey in September 2022. Most of the nurses in the study possessed a MSc/PhD diploma (56.2%) and had previously been infected by SARS-CoV-2 (70.3%). Among nurses, 57.3% were willing to accept the influenza vaccine, 19% were hesitant, and 23.7% were unwilling. Older age, higher levels of perceived support from significant others, and higher COVID-19-related physical exhaustion were positively related to influenza vaccination intention. In contrast, more side effects because of COVID-19 vaccination and higher levels of exhaustion due to measures taken against COVID-19 were negatively associated with vaccination intention. Since the influenza vaccination acceptance rate among nurses was moderate, policymakers should develop and implement measures tailored specifically to nurses in the context of the COVID-19 pandemic to decrease vaccine hesitancy. Full article

(This article belongs to the Special Issue Vaccines Hesitancy and Public Health)

12 pages, 1707 KiB

Open AccessEditor’s ChoiceArticle

SARS-CoV-2 mRNA Dual Immunization Induces Innate Transcriptional Signatures, Establishes T-Cell Memory and Coordinates the Recall Response

by Ioanna Papadatou, Maria Geropeppa, Kleio-Maria Verrou, Marianna Tzanoudaki, Theano Lagousi, Emmanouil Liatsis and Vana Spoulou

Vaccines 2023, 11(1), 103; https://doi.org/10.3390/vaccines11010103 - 1 Jan 2023

Cited by 3 | Viewed by 3264

Abstract

Background: mRNA vaccines have played a crucial role in controlling the SARS-CoV-2 global pandemic. However, the immunological mechanisms involved in the induction, magnitude and longevity of mRNA-vaccine-induced protective immunity are still unclear. Methods: In our study, we used whole-RNA sequencing along with detailed [...] Read more.

Background: mRNA vaccines have played a crucial role in controlling the SARS-CoV-2 global pandemic. However, the immunological mechanisms involved in the induction, magnitude and longevity of mRNA-vaccine-induced protective immunity are still unclear. Methods: In our study, we used whole-RNA sequencing along with detailed immunophenotyping of antigen-specific T cells and humoral RBD-specific response to dual immunization with the Pfizer–BioNTech mRNA vaccine (BNT162b2) and correlated them with response to an additional dose, administered 10 months later, in order to comprehensively profile the immune response of healthy volunteers to BNT162b2. Results: Primary dual immunization induced upregulation of the Type I interferon pathway and generated spike protein (S)-specific IFN-γ+ and TNF-α+ CD4 T cells, S-specific memory CD4 T cells, and RBD-specific antibodies against SARS-CoV-2. S-specific CD4 T cells induced by the primary series correlated with the RBD-specific antibody titers to a third dose. Conclusions: This study demonstrates the induction of both innate and adaptive immunity in response to the BNT162b2 mRNA vaccine in a coordinated manner and identifies the central role of primarily induced CD4+ T cells as a predictive biomarker of the magnitude of anamnestic immune response. Full article

► Show Figures

Figure 1

10 pages, 887 KiB

Open AccessEditor’s ChoiceArticle

Slower Waning of Anti-SARS-CoV-2 IgG Levels Six Months after the Booster Dose Compared to Primary Vaccination

by Sanja Zember, Kristian Bodulić, Nataša Cetinić Balent, Radojka Mikulić, Alemka Markotić and Oktavija Đaković Rode

Vaccines 2022, 10(11), 1813; https://doi.org/10.3390/vaccines10111813 - 28 Oct 2022

Cited by 7 | Viewed by 2161

Abstract

Anti-SARS-CoV-2 IgG titer decreases rapidly after primovaccination, leading to a mandatory booster vaccination. We analysed anti-SARS-CoV-2 Spike RBD IgG levels (positive ≥ 50 AU/mL) in 405 healthcare workers (3010 sera) who received a booster dose (BD) 9 months after two-dose BNT162b2 primovaccination. Median [...] Read more.

Anti-SARS-CoV-2 IgG titer decreases rapidly after primovaccination, leading to a mandatory booster vaccination. We analysed anti-SARS-CoV-2 Spike RBD IgG levels (positive ≥ 50 AU/mL) in 405 healthcare workers (3010 sera) who received a booster dose (BD) 9 months after two-dose BNT162b2 primovaccination. Median antibody titer at the time of BD (582.6 AU/mL) was 1.7-fold and 16.4-fold lower than the peak titer after the first (961.5 AU/mL) and the second vaccine dose (SVD) (10,232.6 AU/mL), respectively. One month after vaccination, IgG titer increased 40.6-fold after BD compared with a 10.8-fold increase after primovaccination. Three months after vaccination, post-booster antibodies decreased significantly slower (2.2-fold) than after primovaccination (3.3-fold). At six months, antibodies decreased slower after BD (4.5-fold; median 5556.0 AU/mL) than after primovaccination (9.6-fold; median 1038.5 AU/mL). Antibody titers before and one month after BD correlated weakly (r = 0.30) compared with a strong correlation (r = 0.65) between the corresponding post-primovaccination titers. Pre-vaccination COVID-19 had no effect on IgG levels after BD compared with a positive effect after primovaccination. Despite high post-booster IgG levels, 22.5% of participants contracted mild COVID-19. The trend of IgG decline indicates the need for further revaccination, but the vaccine type should be defined according to viral mutations. Full article

(This article belongs to the Special Issue Effectiveness, Safety and Immunogenicity of SARS-CoV-2 Vaccines)

► Show Figures

Figure 1

21 pages, 1575 KiB

Open AccessEditor’s ChoiceReview

Antibody-Based Immunotherapies as a Tool for Tackling Multidrug-Resistant Bacterial Infections

by António M. M. Seixas, Sílvia A. Sousa and Jorge H. Leitão

Vaccines 2022, 10(11), 1789; https://doi.org/10.3390/vaccines10111789 - 25 Oct 2022

Cited by 24 | Viewed by 4863

Abstract

The discovery of antimicrobials is an outstanding achievement of mankind that led to the development of modern medicine. However, increasing antimicrobial resistance observed worldwide is rendering commercially available antimicrobials ineffective. This problem results from the bacterial ability to adapt to selective pressure, leading [...] Read more.

The discovery of antimicrobials is an outstanding achievement of mankind that led to the development of modern medicine. However, increasing antimicrobial resistance observed worldwide is rendering commercially available antimicrobials ineffective. This problem results from the bacterial ability to adapt to selective pressure, leading to the development or acquisition of multiple types of resistance mechanisms that can severely affect the efficacy of antimicrobials. The misuse, over-prescription, and poor treatment adherence by patients are factors strongly aggravating this issue, with an epidemic of infections untreatable by first-line therapies occurring over decades. Alternatives are required to tackle this problem, and immunotherapies are emerging as pathogen-specific and nonresistance-generating alternatives to antimicrobials. In this work, four types of antibody formats and their potential for the development of antibody-based immunotherapies against bacteria are discussed. These antibody isotypes include conventional mammalian polyclonal antibodies that are used for the neutralization of toxins; conventional mammalian monoclonal antibodies that currently have 100 IgG mAbs approved for therapeutic use; immunoglobulin Y found in birds and an excellent source of high-quality polyclonal antibodies able to be purified noninvasively from egg yolks; and single domain antibodies (also known as nanobodies), a recently discovered antibody format (found in camelids and nurse sharks) that allows for a low-cost synthesis in microbial systems, access to hidden or hard-to-reach epitopes, and exhibits a high modularity for the development of complex structures. Full article

(This article belongs to the Special Issue Microbial Antigen Identification and Vaccine Delivery Systems)

► Show Figures

Figure 1

17 pages, 298 KiB

Open AccessEditor’s ChoiceReview

COVID-19 Vaccine-Associated Optic Neuropathy: A Systematic Review of 45 Patients

by Ayman G. Elnahry, Mutaz Y. Al-Nawaflh, Aisha A. Gamal Eldin, Omar Solyman, Ahmed B. Sallam, Paul H. Phillips and Abdelrahman M. Elhusseiny

Vaccines 2022, 10(10), 1758; https://doi.org/10.3390/vaccines10101758 - 20 Oct 2022

Cited by 17 | Viewed by 6395

Abstract

We provide a systematic review of published cases of optic neuropathy following COVID-19 vaccination. We used Ovid MEDLINE, PubMed, and Google Scholar. Search terms included: “COVID-19 vaccination”, “optic neuropathy”, “optic neuritis”, and “ischemic optic neuropathy”. The titles and abstracts were screened, then the [...] Read more.

We provide a systematic review of published cases of optic neuropathy following COVID-19 vaccination. We used Ovid MEDLINE, PubMed, and Google Scholar. Search terms included: “COVID-19 vaccination”, “optic neuropathy”, “optic neuritis”, and “ischemic optic neuropathy”. The titles and abstracts were screened, then the full texts were reviewed. Sixty eyes from forty-five patients (28 females) were included. Eighteen eyes from fourteen patients (31.1%) were diagnosed with anterior ischemic optic neuropathy (AION), while 34 eyes from 26 patients (57.8%) were diagnosed with optic neuritis (ON). Other conditions included autoimmune optic neuropathy and Leber hereditary optic neuropathy. Fifteen patients (33.3%) had bilateral involvement. The mean age of all patients was 47.4 ± 17.1 years. The mean age of AION patients was 62.9 ± 12.2 years and of ON patients was 39.7 ± 12.8 years (p < 0.001). The mean time from vaccination to ophthalmic symptoms was 9.6 ± 8.7 days. The mean presenting visual acuity (VA) was logMAR 0.990 ± 0.924. For 41 eyes with available follow-up, the mean presenting VA was logMAR 0.842 ± 0.885, which improved to logMAR 0.523 ± 0.860 at final follow-up (p < 0.001). COVID-19 vaccination may be associated with different forms of optic neuropathy. Patients diagnosed with ON were more likely to be younger and to experience visual improvement. More studies are needed to further characterize optic neuropathies associated with COVID-19 vaccination. Full article

(This article belongs to the Special Issue Ophthalmic Adverse Events following SARS-CoV-2 Vaccination)

11 pages, 1302 KiB

Open AccessEditor’s ChoiceArticle

Relationship between Anti-Spike Antibodies and Risk of SARS-CoV-2 Infection in Infants Born to COVID-19 Vaccinated Mothers

by Madeleine D. Burns, Cordelia Muir, Caroline Atyeo, Jameson P. Davis, Stepan Demidkin, Babatunde Akinwunmi, Alessio Fasano, Kathryn J. Gray, Galit Alter, Lydia L. Shook, Andrea G. Edlow and Lael M. Yonker

Vaccines 2022, 10(10), 1696; https://doi.org/10.3390/vaccines10101696 - 11 Oct 2022

Cited by 17 | Viewed by 3617

Abstract

The goal of this study was to investigate the relationship between anti-SARS-CoV-2-Spike IgG titers passively transferred to the fetus from maternal vaccination during pregnancy and timing of infant SARS-CoV-2 infection. Pregnant, vaccinated individuals (n = 105) and their infants (n = 107) were [...] Read more.

The goal of this study was to investigate the relationship between anti-SARS-CoV-2-Spike IgG titers passively transferred to the fetus from maternal vaccination during pregnancy and timing of infant SARS-CoV-2 infection. Pregnant, vaccinated individuals (n = 105) and their infants (n = 107) were enrolled in a prospective cohort study from July 2021 to June 2022, linking infant anti-Spike IgG titer at birth to risk of SARS-CoV-2 infection in the first fifteen months of life. Cord blood sera were collected at delivery and infant sera were collected at two and six months of age. Anti-SARS-CoV-2-Spike IgG levels were quantified in cord and infant sera using an enzyme-linked immunosorbent assay. Infants were followed for SARS-CoV-2 infection through fifteen months of age. Anti-SARS-CoV-2-Spike IgG titers in infants declined significantly with increased age (p < 0.001). Infants with higher anti-Spike cord blood levels had significantly longer disease-free intervals prior to infection with SARS-CoV-2 (p = 0.027). While higher anti-Spike IgG titer at two months of age was associated with a longer interval to infection through nine months of age (p = 0.073), infant anti-Spike IgG titers by six months of age had no impact on disease-free interval. This cohort study suggests that passively transferred maternal IgG is protective against infant SARS-CoV-2 infection, with higher antibody levels at birth significantly associated with longer disease-free intervals. Infant antibodies and protection from SARS-CoV-2 infection wane significantly after six months, suggesting that vaccination is needed at this stage to optimize protection against COVID-19. Full article

(This article belongs to the Special Issue Research on Immune Response and Vaccines)

► Show Figures

Figure 1

12 pages, 903 KiB

Open AccessEditor’s ChoiceReview

Timing of the First Dose of the Hepatitis B Vaccine in Preterm Infants

by Donna Lei, Taryn Miller, Jeremy Carr, Jim Buttery, Claudia A. Nold-Petry, Marcel F. Nold and Atul Malhotra

Vaccines 2022, 10(10), 1656; https://doi.org/10.3390/vaccines10101656 - 2 Oct 2022

Cited by 8 | Viewed by 3216

Abstract

Introduction: The World Health Organization (WHO) recommends all newborn infants receive the first dose of the hepatitis B vaccine within 24 h of birth irrespective of maternal hepatitis B carrier status. However, the physiological immaturity of the immune system in preterm infants may [...] Read more.

Introduction: The World Health Organization (WHO) recommends all newborn infants receive the first dose of the hepatitis B vaccine within 24 h of birth irrespective of maternal hepatitis B carrier status. However, the physiological immaturity of the immune system in preterm infants may influence the immune responses to the vaccine particularly in the first few days and weeks of life, and adverse events may occur following vaccination that are not observed in infants born at term. Objectives: To review existing published guidelines surrounding timing of the first dose of the hepatitis B vaccine in preterm infants born to hepatitis B surface antigen negative (HBsAg-negative) mothers. Methods: A search was performed for relevant papers and guidelines published between January 2002 and July 2022 on the Ovid MEDLINE and Embase databases and through targeted searches. Two authors independently reviewed the search results to identify relevant sources, which were then analysed and described through narrative synthesis. Results: Twenty-seven relevant papers and guidelines regarding 15 countries and regions were included. Of these, 13.3% of guidelines, which represented 16.8% of the overall population of 4.1 billion people covered by the identified guidelines, recommended a nationwide birth dose of the hepatitis B vaccine to all preterm infants. In 40.0% of guidelines (77.9% of the overall population), the birth dose was only recommended for infants with a birth weight of more than 2000–2200 g. Another 33.3% of countries and regions (covering 4.4% of the population) recommended no universal birth dose for all infants, including preterm infants, whilst 13.3% (1.0% of the population) had guidelines that varied between jurisdictions and hospitals within their country/region. Conclusions: Existing guidelines surrounding the timing of the first dose of the hepatitis B vaccine in preterm infants vary substantially between countries and regions. Further research comparing the immunogenicity and safety of different hepatitis B vaccine schedules is needed to provide concrete evidence to provide guidance regarding the timing of vaccination against hepatitis B in preterm infants. Full article

(This article belongs to the Special Issue Pediatric Infectious Disease and Vaccination)

► Show Figures

Figure 1

14 pages, 339 KiB

Open AccessEditor’s ChoiceReview

A Vaccine for Canine Rocky Mountain Spotted Fever: An Unmet One Health Need

by David H. Walker, Lucas S. Blanton, Maureen Laroche, Rong Fang and Hema P. Narra

Vaccines 2022, 10(10), 1626; https://doi.org/10.3390/vaccines10101626 - 28 Sep 2022

Cited by 10 | Viewed by 3464

Abstract

Outbreaks of life-threatening Rocky Mountain spotted fever in humans and dogs associated with a canine-tick maintenance cycle constitute an important One Health opportunity. The reality of the problem has been observed strikingly in Mexico, Brazil, Colombia, and Native American tribal lands in Arizona. [...] Read more.

Outbreaks of life-threatening Rocky Mountain spotted fever in humans and dogs associated with a canine-tick maintenance cycle constitute an important One Health opportunity. The reality of the problem has been observed strikingly in Mexico, Brazil, Colombia, and Native American tribal lands in Arizona. The brown dog tick, Rhipicephalus sanguineus sensu lato, acquires the rickettsia from bacteremic dogs and can maintain the bacterium transtadially to the next tick stage. The subsequent adult tick can then transmit infection to a new host, as shown by guinea pig models. These brown dog ticks maintain spotted fever group rickettsiae transovarially through many generations, thus serving as both vector and reservoir. Vaccine containing whole-killed R. rickettsii does not stimulate sufficient immunity. Studies of Rickettsia subunit antigens have demonstrated that conformationally preserved outer-membrane autotransporter proteins A and B are the leading vaccine candidates. The possibility of a potentially safe and effective live attenuated vaccine has only begun to be explored as gene knockout methods are applied to these obligately intracellular pathogens. Full article

(This article belongs to the Special Issue Immunity and Vaccination against Bacterial Infections)

17 pages, 668 KiB

Open AccessEditor’s ChoiceArticle

Determinants of Antibody Responses to SARS-CoV-2 Vaccines: Population-Based Longitudinal Study (COVIDENCE UK)

by David A. Jolliffe, Sian E. Faustini, Hayley Holt, Natalia Perdek, Sheena Maltby, Mohammad Talaei, Matthew Greenig, Giulia Vivaldi, Florence Tydeman, Jane Symons, Gwyneth A. Davies, Ronan A. Lyons, Christopher J. Griffiths, Frank Kee, Aziz Sheikh, Seif O. Shaheen, Alex G. Richter and Adrian R. Martineau

Vaccines 2022, 10(10), 1601; https://doi.org/10.3390/vaccines10101601 - 23 Sep 2022

Cited by 25 | Viewed by 4204

Abstract

Antibody responses to SARS-CoV-2 vaccines vary for reasons that remain poorly understood. A range of sociodemographic, behavioural, clinical, pharmacologic and nutritional factors could explain these differences. To investigate this hypothesis, we tested for presence of combined IgG, IgA and IgM (IgGAM) anti-Spike antibodies [...] Read more.

Antibody responses to SARS-CoV-2 vaccines vary for reasons that remain poorly understood. A range of sociodemographic, behavioural, clinical, pharmacologic and nutritional factors could explain these differences. To investigate this hypothesis, we tested for presence of combined IgG, IgA and IgM (IgGAM) anti-Spike antibodies before and after 2 doses of ChAdOx1 nCoV-19 (ChAdOx1, AstraZeneca) or BNT162b2 (Pfizer-BioNTech) in UK adults participating in a population-based longitudinal study who received their first dose of vaccine between December 2020 and July 2021. Information on sixty-six potential sociodemographic, behavioural, clinical, pharmacologic and nutritional determinants of serological response to vaccination was captured using serial online questionnaires. We used logistic regression to estimate multivariable-adjusted odds ratios (aORs) for associations between independent variables and risk of seronegativity following two vaccine doses. Additionally, percentage differences in antibody titres between groups were estimated in the sub-set of participants who were seropositive post-vaccination using linear regression. Anti-spike antibodies were undetectable in 378/9101 (4.2%) participants at a median of 8.6 weeks post second vaccine dose. Increased risk of post-vaccination seronegativity associated with administration of ChAdOx1 vs. BNT162b2 (adjusted odds ratio (aOR) 6.6, 95% CI 4.2–10.4), shorter interval between vaccine doses (aOR 1.6, 1.2–2.1, 6–10 vs. >10 weeks), poor vs. excellent general health (aOR 3.1, 1.4–7.0), immunodeficiency (aOR 6.5, 2.5–16.6) and immunosuppressant use (aOR 3.7, 2.4–5.7). Odds of seronegativity were lower for participants who were SARS-CoV-2 seropositive pre-vaccination (aOR 0.2, 0.0–0.6) and for those taking vitamin D supplements (aOR 0.7, 0.5–0.9). Serologic responses to vaccination did not associate with time of day of vaccine administration, lifestyle factors including tobacco smoking, alcohol intake and sleep, or use of anti-pyretics for management of reactive symptoms after vaccination. In a sub-set of 8727 individuals who were seropositive post-vaccination, lower antibody titres associated with administration of ChAdOx1 vs. BNT162b2 (43.4% lower, 41.8–44.8), longer duration between second vaccine dose and sampling (12.7% lower, 8.2–16.9, for 9–16 weeks vs. 2–4 weeks), shorter interval between vaccine doses (10.4% lower, 3.7–16.7, for <6 weeks vs. >10 weeks), receiving a second vaccine dose in October–December vs. April–June (47.7% lower, 11.4–69.1), older age (3.3% lower per 10-year increase in age, 2.1–4.6), and hypertension (4.1% lower, 1.1–6.9). Higher antibody titres associated with South Asian ethnicity (16.2% higher, 3.0–31.1, vs. White ethnicity) or Mixed/Multiple/Other ethnicity (11.8% higher, 2.9–21.6, vs. White ethnicity), higher body mass index (BMI; 2.9% higher, 0.2–5.7, for BMI 25–30 vs. <25 kg/m²) and pre-vaccination seropositivity for SARS-CoV-2 (105.1% higher, 94.1–116.6, for those seropositive and experienced COVID-19 symptoms vs. those who were seronegative pre-vaccination). In conclusion, we identify multiple determinants of antibody responses to SARS-CoV-2 vaccines, many of which are modifiable. Full article

(This article belongs to the Special Issue Antibody Response of Vaccines to SARS-CoV-2)

► Show Figures

Figure 1

10 pages, 1674 KiB

Open AccessEditor’s ChoiceArticle

Antibody Titers and Protection against Omicron (BA.1 and BA.2) SARS-CoV-2 Infection

by Chloé Dimeglio, Marion Migueres, Naémie Bouzid, Sabine Chapuy-Regaud, Caroline Gernigon, Isabelle Da-Silva, Marion Porcheron, Guillaume Martin-Blondel, Fabrice Herin and Jacques Izopet

Vaccines 2022, 10(9), 1548; https://doi.org/10.3390/vaccines10091548 - 17 Sep 2022

Cited by 30 | Viewed by 2910

Abstract

The emergence of the SARS-CoV-2 variants of concern has greatly influenced the immune correlates of protection, and there are little data about the antibody threshold concentrations to protect against infection with SARS-CoV-2 Omicron BA.1 or BA.2. We analyzed the antibody responses of 259 [...] Read more.

The emergence of the SARS-CoV-2 variants of concern has greatly influenced the immune correlates of protection, and there are little data about the antibody threshold concentrations to protect against infection with SARS-CoV-2 Omicron BA.1 or BA.2. We analyzed the antibody responses of 259 vaccinated healthcare workers, some of whom had been previously infected by SARS-CoV-2. The median follow-up was 179 days (IQR: 171–182) after blood collection. We detected 88 SARS-CoV-2 Omicron infections during the follow-up period, 55 (62.5%) with SARS-CoV-2 BA.1, and 33 (37.5%) with SARS-CoV-2 BA.2. A neutralizing antibody titer below 8 provided no protection against a BA.1 infection, a titer of 16 or 32 gave 73.2% protection, and a titer of 64 or 128 provided 78.4% protection. Conversely, the BA.2 infection rate did not vary as a function of anti-BA.2 neutralizing antibody titers. Binding antibody concentrations below 6000 BAU/mL provided no protection against Omicron BA.1 infection, 6000–20,000 BAU/mL provided 55.6% protection, and 20,000 or more provided 87.7% protection. There was no difference in BA.2 infection depending on the binding antibody concentration. Further studies are needed to investigate the relationship between antibody concentrations and infection with the Omicron BA.4/5 variants that are becoming predominant worldwide. Full article

(This article belongs to the Special Issue Influence of Natural and/or Vaccine Immunity on the Dynamics of SARS-CoV-2)

► Show Figures

Figure 1

18 pages, 4289 KiB

Open AccessEditor’s ChoiceArticle

Microneedle Delivery of an Adjuvanted Microparticulate Vaccine Induces High Antibody Levels in Mice Vaccinated against Coronavirus

by Sharon Vijayanand, Smital Patil, Devyani Joshi, Ipshita Menon, Keegan Braz Gomes, Akanksha Kale, Priyal Bagwe, Shadi Yacoub, Mohammad N. Uddin and Martin J. D’Souza

Vaccines 2022, 10(9), 1491; https://doi.org/10.3390/vaccines10091491 - 7 Sep 2022

Cited by 15 | Viewed by 3972

Abstract

This ‘proof-of-concept’ study aimed to test the microparticulate vaccine delivery system and a transdermal vaccine administration strategy using dissolving microneedles (MN). For this purpose, we formulated poly(lactic-co-glycolic) acid (PLGA) microparticles (MP) encapsulating the inactivated canine coronavirus (iCCoV), as a model antigen, along with [...] Read more.

This ‘proof-of-concept’ study aimed to test the microparticulate vaccine delivery system and a transdermal vaccine administration strategy using dissolving microneedles (MN). For this purpose, we formulated poly(lactic-co-glycolic) acid (PLGA) microparticles (MP) encapsulating the inactivated canine coronavirus (iCCoV), as a model antigen, along with adjuvant MP encapsulating Alhydrogel^® and AddaVax. We characterized the vaccine MP for size, surface charge, morphology, and encapsulation efficiency. Further, we evaluated the in vitro immunogenicity, cytotoxicity, and antigen-presentation of vaccine/adjuvant MP in murine dendritic cells (DCs). Additionally, we tested the in vivo immunogenicity of the MP vaccine in mice through MN administration. We evaluated the serum IgG, IgA, IgG1, and IgG2a responses using an enzyme-linked immunosorbent assay. The results indicate that the particulate form of the vaccine is more immunogenic than the antigen suspension in vitro. We found the vaccine/adjuvant MP to be non-cytotoxic to DCs. The expression of antigen-presenting molecules, MHC I/II, and their costimulatory molecules, CD80/40, increased with the addition of the adjuvants. Moreover, the results suggest that the MP vaccine is cross presented by the DCs. In vivo, the adjuvanted MP vaccine induced increased antibody levels in mice following vaccination and will further be assessed for its cell-mediated responses. Full article

(This article belongs to the Special Issue Novel Vaccine Stabilization and Delivery Technologies)

► Show Figures

Graphical abstract

8 pages, 265 KiB

Open AccessEditor’s ChoiceArticle

Differences in Long-COVID Symptoms between Vaccinated and Non-Vaccinated (BNT162b2 Vaccine) Hospitalized COVID-19 Survivors Infected with the Delta Variant

by César Fernández-de-las-Peñas, Ricardo Ortega-Santiago, Stella Fuensalida-Novo, José D. Martín-Guerrero, Oscar J. Pellicer-Valero and Juan Torres-Macho

Vaccines 2022, 10(9), 1481; https://doi.org/10.3390/vaccines10091481 - 6 Sep 2022

Cited by 18 | Viewed by 4762

Abstract

This study compared differences in the presence of post-COVID symptoms among vaccinated and non-vaccinated COVID-19 survivors requiring hospitalization due to the Delta (B.1.617.2) variant. This cohort study included hospitalized subjects who had survived SARS-CoV-2 infection (Delta variant) from July to August 2021 in [...] Read more.

This study compared differences in the presence of post-COVID symptoms among vaccinated and non-vaccinated COVID-19 survivors requiring hospitalization due to the Delta (B.1.617.2) variant. This cohort study included hospitalized subjects who had survived SARS-CoV-2 infection (Delta variant) from July to August 2021 in an urban hospital in Madrid, Spain. Individuals were classified as vaccinated if they received full administration (i.e., two doses) of BNT162b2 (“Pfizer-BioNTech”) vaccines. Other vaccines were excluded. Those with just one dose of the BNT162b2 vaccine were considered as non-vaccinated. Patients were scheduled for a telephone interview at a follow-up around six months after infection for assessing the presence of post-COVID symptoms with particular attention to those symptoms starting after acute infection and hospitalization. Anxiety/depressive levels and sleep quality were likely assessed. Hospitalization and clinical data were collected from medical records. A total comprising 109 vaccinated and 92 non-vaccinated COVID-19 survivors was included. Vaccinated patients were older and presented a higher number of medical comorbidities, particular cardiorespiratory conditions, than non-vaccinated patients. No differences in COVID-19 onset symptoms at hospitalization and post-COVID symptoms six months after hospital discharge were found between vaccinated and non-vaccinated groups. No specific risk factor for any post-COVID symptom was identified in either group. This study observed that COVID-19 onset-associated symptoms and post-COVID symptoms six-months after hospitalization were similar between previously hospitalized COVID-19 survivors vaccinated and those non-vaccinated. Current data can be applied to the Delta variant and those vaccinated with BNT162b2 (Pfizer-BioNTech) vaccine. Full article

(This article belongs to the Special Issue Assessment of Post-COVID-19 Complications and Vaccination Efficacy)

10 pages, 1092 KiB

Open AccessEditor’s ChoiceArticle

Correlation between Adverse Events and Antibody Titers among Healthcare Workers Vaccinated with BNT162b2 mRNA COVID-19 Vaccine

by Itzchak Levy, Einav Gal Levin, Liraz Olmer, Gili Regev-Yochay, Nancy Agmon-Levin, Anat Wieder-Finesod, Victoria Indenbaum, Karin Herzog, Ram Doolman, Keren Asraf, Rebecca Halperin, Yaniv Lustig and Galia Rahav

Vaccines 2022, 10(8), 1220; https://doi.org/10.3390/vaccines10081220 - 30 Jul 2022

Cited by 18 | Viewed by 2968

Abstract

Objectives: The BNT162b2 mRNA COVID-19 vaccine has been found to be highly effective in preventing COVID-19 but is associated with increased reactogenicity. We aimed to examine the correlation between immunogenicity and reactogenicity of the BNT162b2 vaccine. Methods: Subjects without prior SARS-CoV-2 infection that [...] Read more.

Objectives: The BNT162b2 mRNA COVID-19 vaccine has been found to be highly effective in preventing COVID-19 but is associated with increased reactogenicity. We aimed to examine the correlation between immunogenicity and reactogenicity of the BNT162b2 vaccine. Methods: Subjects without prior SARS-CoV-2 infection that participated in active surveillance after being vaccinated with the BNT162b2 vaccine were included. Study participants reported adverse drug reactions (ADRs) through questionnaires administered by text message after receiving each dose of the vaccine. A reactogenicity score was developed based on the type and duration of ADRs. In addition, anti-receptor binding domain (RBD) levels and neutralization assays were performed 7–21 and 7–38 days after the first and second vaccine doses, respectively. Associations between ADRs and antibody levels were assessed by Spearman correlations. Multivariable logistic regression analyses were used to identify factors associated with ADRs. Results: A total of 831 health care workers were included. The mean age was 46.5 years (SD = 11.8) and 75.5% were females. 83.4% and 83.3% had at least one local ADR after the first and second doses, respectively. 33% and 83.2% had at least one systemic ADR after the first and second doses, respectively. Multivariate logistic regression analysis found a significant correlation between ADR score and anti-RBD-IgG titers (r = 0.366; p < 0.0001) after adjustment for age, gender, and days after the second vaccination. High anti-RBD-IgG levels, being younger than 55 and being female, were all correlated with increased rates of ADRs. Conclusion: BNT162b2 mRNA COVID-19 vaccine reactogenicity appears to be correlated with higher post-vaccination antibody levels and is independently associated with younger age and female gender. Full article

► Show Figures

Figure 1

16 pages, 746 KiB

Open AccessEditor’s ChoiceReview

COVID-19 Vaccine Booster Strategies for Omicron SARS-CoV-2 Variant: Effectiveness and Future Prospects

by Dorota Zarębska-Michaluk, Chenlin Hu, Michał Brzdęk, Robert Flisiak and Piotr Rzymski

Vaccines 2022, 10(8), 1223; https://doi.org/10.3390/vaccines10081223 - 30 Jul 2022

Cited by 17 | Viewed by 18290

Abstract

In the light of the lack of authorized COVID-19 vaccines adapted to the Omicron variant lineage, the administration of the first and second booster dose is recommended. It remains important to monitor the efficacy of such an approach in order to inform future [...] Read more.

In the light of the lack of authorized COVID-19 vaccines adapted to the Omicron variant lineage, the administration of the first and second booster dose is recommended. It remains important to monitor the efficacy of such an approach in order to inform future preventive strategies. The present paper summarizes the research progress on the effectiveness of the first and second booster doses of COVID-19. It also discusses the potential approach in vaccination strategies that could be undertaken to maintain high levels of protection during the waves of SARS-CoV-2 infections. Although this approach can be based, with some shortcomings, on the first-generation vaccines, other vaccination strategies should be explored, including developing multiple antigen-based (multivariant-adapted) booster doses with enhanced durability of immune protection, e.g., through optimization of the half-life of generated antibodies. Full article

► Show Figures

Figure 1

17 pages, 1850 KiB

Open AccessEditor’s ChoiceReview

Safety and Efficacy of Influenza Vaccination in Patients Receiving Immune Checkpoint Inhibitors. Systematic Review with Meta-Analysis

by Maria A. Lopez-Olivo, Valeria Valerio, Aliza R. Karpes Matusevich, Marianela Brizio, Michelle Kwok, Yimin Geng, Maria E. Suarez-Almazor and Ines Colmegna

Vaccines 2022, 10(8), 1195; https://doi.org/10.3390/vaccines10081195 - 27 Jul 2022

Cited by 19 | Viewed by 2829

Abstract

The potential increased risk of immune-related adverse events (irAEs) post-influenza vaccine is a concern in patients receiving immune checkpoint inhibitors (ICI). We conducted a systematic review with meta-analysis of studies reporting the effects of influenza vaccination in patients with cancer during ICI treatment. [...] Read more.

The potential increased risk of immune-related adverse events (irAEs) post-influenza vaccine is a concern in patients receiving immune checkpoint inhibitors (ICI). We conducted a systematic review with meta-analysis of studies reporting the effects of influenza vaccination in patients with cancer during ICI treatment. We searched five electronic databases until 01/2022. Two authors independently selected studies, appraised their quality, and collected data. The primary outcome was the determination of pooled irAE rates. Secondary outcomes included determination of immunogenicity and influenza infection rates and cancer-related outcomes. Nineteen studies (26 publications, n = 4705) were included; 89.5% were observational. Vaccinated patients reported slighter lower rates of irAEs compared to unvaccinated patients (32% versus 41%, respectively). Seroprotection for influenza type A was 78%–79%, and for type B was 75%. Influenza and irAE-related death rates were similar between groups. The pooled proportion of participants reporting a laboratory-confirmed infection was 2% (95% CI 0% to 6%), and influenza-like illness was 14% (95% CI 2% to 32%). No differences were reported on the rates of laboratory-confirmed infection between vaccinated and unvaccinated patients. Longer progression-free and overall survival was also observed in vaccinated compared with unvaccinated patients. Current evidence suggests that influenza vaccination is safe in patients receiving ICIs, does not increase the risk of irAEs, and may improve survival. Full article

(This article belongs to the Section Influenza Virus Vaccines)

► Show Figures

Figure 1

27 pages, 1796 KiB

Open AccessEditor’s ChoiceReview

Nanoparticle- and Microparticle-Based Vaccines against Orbiviruses of Veterinary Importance

by Luis Jiménez-Cabello, Sergio Utrilla-Trigo, Natalia Barreiro-Piñeiro, Tomás Pose-Boirazian, José Martínez-Costas, Alejandro Marín-López and Javier Ortego

Vaccines 2022, 10(7), 1124; https://doi.org/10.3390/vaccines10071124 - 14 Jul 2022

Cited by 11 | Viewed by 4308

Abstract

Bluetongue virus (BTV) and African horse sickness virus (AHSV) are widespread arboviruses that cause important economic losses in the livestock and equine industries, respectively. In addition to these, another arthropod-transmitted orbivirus known as epizootic hemorrhagic disease virus (EHDV) entails a major threat as [...] Read more.

Bluetongue virus (BTV) and African horse sickness virus (AHSV) are widespread arboviruses that cause important economic losses in the livestock and equine industries, respectively. In addition to these, another arthropod-transmitted orbivirus known as epizootic hemorrhagic disease virus (EHDV) entails a major threat as there is a conducive landscape that nurtures its emergence in non-endemic countries. To date, only vaccinations with live attenuated or inactivated vaccines permit the control of these three viral diseases, although important drawbacks, e.g., low safety profile and effectiveness, and lack of DIVA (differentiation of infected from vaccinated animals) properties, constrain their usage as prophylactic measures. Moreover, a substantial number of serotypes of BTV, AHSV and EHDV have been described, with poor induction of cross-protective immune responses among serotypes. In the context of next-generation vaccine development, antigen delivery systems based on nano- or microparticles have gathered significant attention during the last few decades. A diversity of technologies, such as virus-like particles or self-assembled protein complexes, have been implemented for vaccine design against these viruses. In this work, we offer a comprehensive review of the nano- and microparticulated vaccine candidates against these three relevant orbiviruses. Additionally, we also review an innovative technology for antigen delivery based on the avian reovirus nonstructural protein muNS and we explore the prospective functionality of the nonstructural protein NS1 nanotubules as a BTV-based delivery platform. Full article

(This article belongs to the Special Issue Microparticle-Based Vaccines)

► Show Figures

Figure 1

18 pages, 1381 KiB

Open AccessEditor’s ChoiceReview

Pseudomonas aeruginosa: Recent Advances in Vaccine Development

by Matthew Killough, Aoife Maria Rodgers and Rebecca Jo Ingram

Vaccines 2022, 10(7), 1100; https://doi.org/10.3390/vaccines10071100 - 8 Jul 2022

Cited by 48 | Viewed by 16582

Abstract

Pseudomonas aeruginosa is an important opportunistic human pathogen. Using its arsenal of virulence factors and its intrinsic ability to adapt to new environments, P. aeruginosa causes a range of complicated acute and chronic infections in immunocompromised individuals. Of particular importance are burn wound [...] Read more.

Pseudomonas aeruginosa is an important opportunistic human pathogen. Using its arsenal of virulence factors and its intrinsic ability to adapt to new environments, P. aeruginosa causes a range of complicated acute and chronic infections in immunocompromised individuals. Of particular importance are burn wound infections, ventilator-associated pneumonia, and chronic infections in people with cystic fibrosis. Antibiotic resistance has rendered many of these infections challenging to treat and novel therapeutic strategies are limited. Multiple clinical studies using well-characterised virulence factors as vaccine antigens over the last 50 years have fallen short, resulting in no effective vaccination being available for clinical use. Nonetheless, progress has been made in preclinical research, namely, in the realms of antigen discovery, adjuvant use, and novel delivery systems. Herein, we briefly review the scope of P. aeruginosa clinical infections and its major important virulence factors. Full article

(This article belongs to the Section Vaccines against Tropical and other Infectious Diseases)

► Show Figures

Figure 1

16 pages, 1433 KiB

Open AccessEditor’s ChoiceArticle

Correlates of Zero-Dose Vaccination Status among Children Aged 12–59 Months in Sub-Saharan Africa: A Multilevel Analysis of Individual and Contextual Factors

by Chamberline E. Ozigbu, Bankole Olatosi, Zhenlong Li, James W. Hardin and Nicole L. Hair

Vaccines 2022, 10(7), 1052; https://doi.org/10.3390/vaccines10071052 - 30 Jun 2022

Cited by 21 | Viewed by 4213

Abstract

Despite ongoing efforts to improve childhood vaccination coverage, including in hard-to-reach and hard-to-vaccinate communities, many children in sub-Saharan Africa (SSA) remain unvaccinated. Considering recent goals set by the Immunization Agenda 2030 (IA2030), including reducing the number of zero-dose children by half, research that [...] Read more.

Despite ongoing efforts to improve childhood vaccination coverage, including in hard-to-reach and hard-to-vaccinate communities, many children in sub-Saharan Africa (SSA) remain unvaccinated. Considering recent goals set by the Immunization Agenda 2030 (IA2030), including reducing the number of zero-dose children by half, research that goes beyond coverage to identify populations and groups at greater risk of being unvaccinated is urgently needed. This is a pooled cross-sectional study of individual- and country-level data obtained from Demographic and Health Surveys Program and two open data repositories. The sample includes 43,131 children aged 12–59 months sampled between 2010 and 2020 in 33 SSA countries. Associations of zero-dose status with individual and contextual factors were assessed using multilevel logistic regression. 16.5% of children had not received any vaccines. Individual level factors associated lower odds of zero-dose status included mother’s primary school or high school education, employment, use of antenatal care services and household wealth. Compared to children in countries with lower GDP, children in countries with relatively high GDP had nearly four times greater odds of being unvaccinated. Both individual and contextual factors are correlated with zero-dose status in SSA. Our results can inform efforts to identify and reach children who have not received any vaccines. Full article

(This article belongs to the Special Issue Immunization of Children and Women against Infectious Diseases)

► Show Figures

Figure 1

15 pages, 2305 KiB

Open AccessEditor’s ChoiceArticle

A Cloned Recombinant Vesicular Stomatitis Virus-Vectored Marburg Vaccine, PHV01, Protects Guinea Pigs from Lethal Marburg Virus Disease

by Wenjun Zhu, Guodong Liu, Wenguang Cao, Shihua He, Anders Leung, Ute Ströher, Michael J. Fairchild, Rick Nichols, Joseph Crowell, Joan Fusco and Logan Banadyga

Vaccines 2022, 10(7), 1004; https://doi.org/10.3390/vaccines10071004 - 23 Jun 2022

Cited by 15 | Viewed by 3262

Abstract

Marburg virus (MARV) is a negative-sense, single-stranded RNA virus that belongs to the Filoviridae family. Despite having caused numerous outbreaks of severe hemorrhagic fever with high case fatality rates, there are still no clinically approved therapeutics or vaccines to treat or prevent MARV [...] Read more.

Marburg virus (MARV) is a negative-sense, single-stranded RNA virus that belongs to the Filoviridae family. Despite having caused numerous outbreaks of severe hemorrhagic fever with high case fatality rates, there are still no clinically approved therapeutics or vaccines to treat or prevent MARV disease. Recombinant vesicular stomatitis viruses (rVSVs) expressing heterologous viral glycoproteins have shown remarkable promise as live-attenuated vaccine vectors, with an rVSV-based Ebola virus vaccine having received regulatory approval in the United States and numerous other countries. Analogous rVSV vaccine vectors have also been developed for MARV and have shown efficacy in several preclinical studies conducted in nonhuman primates. Here, we used a guinea pig model to confirm the protective efficacy of a cloned, rVSV-based candidate vaccine, termed PHV01, expressing the MARV variant Angola glycoprotein. Our results demonstrated that a single dose (2 × 10⁶ PFU) of vaccine administered 28 days prior to challenge with a uniformly lethal dose of guinea-pig-adapted MARV variant Angola provided complete protection from death and disease. Moreover, protection was robust, with as little as 200 PFU of vaccine conferring significant protection. Not only does this study highlight the potential predictive value of the guinea pig model in the evaluation of MARV countermeasures, but it also demonstrates consistent and reproducible protection afforded by a clonal vaccine candidate. Indeed, this study identifies PHV01 as a suitable vaccine candidate for advanced development. Full article

(This article belongs to the Special Issue Vaccine Development Needs for Marburg Virus and Sudan Ebolavirus: Leveraging Lessons Learned from the Zaire Ebolavirus)

► Show Figures

Figure 1

19 pages, 373 KiB

Open AccessEditor’s ChoiceReview

Vaccine Preventable Zoonotic Diseases: Challenges and Opportunities for Public Health Progress

by Ann Carpenter, Michelle A. Waltenburg, Aron Hall, James Kile, Marie Killerby, Barbara Knust, Maria Negron, Megin Nichols, Ryan M. Wallace, Casey Barton Behravesh, Jennifer H. McQuiston and the Vaccine Preventable Zoonotic Disease Working Group

Vaccines 2022, 10(7), 993; https://doi.org/10.3390/vaccines10070993 - 22 Jun 2022

Cited by 29 | Viewed by 8431

Abstract

Zoonotic diseases represent a heavy global burden, causing important economic losses, impacting animal health and production, and costing millions of human lives. The vaccination of animals and humans to prevent inter-species zoonotic disease transmission is an important intervention. However, efforts to develop and [...] Read more.

Zoonotic diseases represent a heavy global burden, causing important economic losses, impacting animal health and production, and costing millions of human lives. The vaccination of animals and humans to prevent inter-species zoonotic disease transmission is an important intervention. However, efforts to develop and implement vaccine interventions to reduce zoonotic disease impacts are often limited to the veterinary and agricultural sectors and do not reflect the shared burden of disease. Multisectoral collaboration, including co-development opportunities for human and animal vaccines, expanding vaccine use to include animal reservoirs such as wildlife, and strategically using vaccines to interrupt complex transmission cycles is needed. Addressing zoonoses requires a multi-faceted One Health approach, wherein vaccinating people and animals plays a critical role. Full article

(This article belongs to the Special Issue Veterinary Vaccines and One Health)

15 pages, 1010 KiB

Open AccessEditor’s ChoiceArticle

Predictors of Immunogenic Response to the BNT162b2 mRNA COVID-19 Vaccination in Patients with Autoimmune Inflammatory Rheumatic Diseases Treated with Rituximab

by Victoria Furer, Tali Eviatar, Devy Zisman, Hagit Peleg, Yolanda Braun-Moscovici, Alexandra Balbir-Gurman, Daphna Paran, David Levartovsky, Michael Zisapel, Ofir Elalouf, Ilana Kaufman, Adi Broyde, Ari Polachek, Joy Feld, Amir Haddad, Tal Gazitt, Muna Elias, Nizar Higazi, Fadi Kharouf, Sara Pel, Sharon Nevo and Ori Elkayam Show full author list Hide full author list

Vaccines 2022, 10(6), 901; https://doi.org/10.3390/vaccines10060901 - 6 Jun 2022

Cited by 22 | Viewed by 3225

Abstract

Treatment with rituximab (RTX) blunts SARS-CoV-2 vaccination-induced humoral response. We sought to identify predictors of a positive immunogenic response to the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases (AIIRD) treated with RTX (AIIRD-RTX). We analyzed 108 AIIRD-RTX patients and 122 [...] Read more.

Treatment with rituximab (RTX) blunts SARS-CoV-2 vaccination-induced humoral response. We sought to identify predictors of a positive immunogenic response to the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases (AIIRD) treated with RTX (AIIRD-RTX). We analyzed 108 AIIRD-RTX patients and 122 immunocompetent controls vaccinated with BNT162b2 mRNA participating in a multicenter vaccination study. Immunogenicity was defined by positive anti-SARS-CoV-2 S1/S2 IgG. We used a stepwise backward multiple logistic regression to identify predicting factors for a positive immunogenic response to vaccination and develop a predicting calculator, further validated in an independent cohort of AIIRD-RTX BNT162b2 mRNA vaccinated patients (n = 48). AIIRD-RTX patients who mounted a seropositive immunogenic response significantly differed from patients who did not by a lower number of RTX courses (median (range) 3 (1–10) vs. 5 (1–15), p = 0.007; lower cumulative RTX dose (mean ± SD) 6943.11 ± 5975.74 vs. 9780.95 ± 7240.12 mg, p = 0.033; higher IgG level prior to last RTX course (mean ± SD), 1189.78 ± 576.28 vs. 884.33 ± 302.31 mg/dL, p = 0.002), and extended interval between RTX treatment and vaccination, 469.82 ± 570.39 vs. 162.08 ± 160.12 days, p = 0.0009, respectively. Patients with ANCA-associated vasculitis and inflammatory myositis had a low likelihood of a seropositive immunogenic response compared to patients with rheumatoid arthritis, odds ratio (OR) 0.209, 95% confidence interval (CI) 0.046–0.96, p = 0.044 and OR 0.189, 95% CI 0.036–0.987, p = 0.048, respectively. Based on these findings, we constructed a calculator predicting the probability of a seropositive immunogenic response following BNT162b2 mRNA vaccination which performed with 90.5% sensitivity, 59.3% specificity, and 63.3% positive and 88.9% negative predictive values. In summary, the predicting calculator could guide clinicians for optimal timing of BNT162b2 mRNA vaccination in AIIRD-RTX patients. Full article

(This article belongs to the Topic Global Analysis of SARS-CoV-2 Serology)

► Show Figures

Figure 1

26 pages, 748 KiB

Open AccessEditor’s ChoiceReview

An Overview of Vaccine Adjuvants: Current Evidence and Future Perspectives

by Alessio Facciolà, Giuseppa Visalli, Antonio Laganà and Angela Di Pietro

Vaccines 2022, 10(5), 819; https://doi.org/10.3390/vaccines10050819 - 22 May 2022

Cited by 167 | Viewed by 27341

Abstract

Vaccinations are one of the most important preventive tools against infectious diseases. Over time, many different types of vaccines have been developed concerning the antigen component. Adjuvants are essential elements that increase the efficacy of vaccination practises through many different actions, especially acting [...] Read more.

Vaccinations are one of the most important preventive tools against infectious diseases. Over time, many different types of vaccines have been developed concerning the antigen component. Adjuvants are essential elements that increase the efficacy of vaccination practises through many different actions, especially acting as carriers, depots, and stimulators of immune responses. For many years, few adjuvants have been included in vaccines, with aluminium salts being the most commonly used adjuvant. However, recent research has focused its attention on many different new compounds with effective adjuvant properties and improved safety. Modern technologies such as nanotechnologies and molecular biology have forcefully entered the production processes of both antigen and adjuvant components, thereby improving vaccine efficacy. Microparticles, emulsions, and immune stimulators are currently in the spotlight for their huge potential in vaccine production. Although studies have reported some potential side effects of vaccine adjuvants such as the recently recognised ASIA syndrome, the huge worth of vaccines remains unquestionable. Indeed, the recent COVID-19 pandemic has highlighted the importance of vaccines, especially in regard to managing future potential pandemics. In this field, research into adjuvants could play a leading role in the production of increasingly effective vaccines. Full article

(This article belongs to the Special Issue Present and Future Vaccinations: Current Strategies and New Perspectives in the Fight against Infectious Diseases)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Editor’s Choice Articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI